Moorestown, New Jersey, United States
biotecMAX™ Feb/Mar/APR/May 2022 Insight
Cosentyx® (secukinumab)
Novartis Cosentyx® (secukinumab) receives positive CHMP opinion for expanded use in childhood arthritic conditions
May 20, 2022
- Positive opinion could expand the role of Cosentyx®(secukinumab) in reducing flare risk in pediatric enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA) patients in the EU
- Safety in these pediatric populations was consistent with the known safety profile across approved adult and pediatric indications
- Since its initial approval, Cosentyx has a proven sustained efficacy profile across several systemic inflammatory conditions and has treated more than 700,000 patients worldwide 1-11
Basel, May 20, 2022 — Novartis today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion for Cosentyx® (secukinumab), used alone or in combination with methotrexate, in the juvenile idiopathic arthritis (JIA) categories of enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) in patients 6 years and older whose disease has responded inadequately to, or who cannot tolerate, conventional therapy8.
“JIA is the most common childhood rheumatic disease, affecting millions of children worldwide. Unfortunately, due to the limitations of current or available treatment options, some patients continue to experience symptoms, with an impact on their life. If approved in Europe, Cosentyx could offer a much-needed, additional effective treatment for the underserved ERA and JPsA patient populations,” said Ivan Foeldvari, M.D., Hamburg Centre for Pediatric Rheumatology, Germany.
ERA and JPsA are progressive, debilitating autoimmune diseases12-14. ERA is characterized by joint swelling and pain where tendons and ligaments attach to bone and may present with lower back pain or tenderness at the palpation of the hips13-15. JPsA is characterized by joint swelling and skin psoriasis and may present with nail changes, inflammation of fingers and/or toes or psoriatic skin changes in a first-degree relative. If left untreated, they can lead to high levels of pain and disability12-15.
“The positive CHMP opinion reinforces that children and adults living with immunologic rheumatic and dermatological diseases, and the physicians who treat them, may feel confident in the management of these diseases with Cosentyx,” said Todd Fox, Global Head of Medical Affairs Immunology at Novartis. “We’re committed to bringing innovative treatments to young people living with rheumatic diseases across the world. With recent approvals in the US, Japan and Brazil, we are one step closer in our ambition to expand Cosentyx to 10 indications in areas of high unmet need.”
The positive CHMP opinion is based on data from the Phase III JUNIPERA study, a 2-year, three-part, double-blind, placebo-controlled, randomized withdrawal trial showing significantly longer time to flare in Cosentyx vs placebo (P<.001) in pediatric ERA and JPsA patients16. Safety in this pediatric population was consistent with the known safety profile of Cosentyx across approved adult and pediatric indications9.
This CHMP recommendation supports Novartis ongoing commitment to the pediatric community across a range of inflammatory conditions. In July 2020, Cosentyx received EMA approval as a first-line systemic treatment for pediatric psoriasis in patients aged 6-18 years old and recently received approval in the US and China8, 17. In 2021, Cosentyx was also approved in Japan to treat both PsA and psoriasis in pediatric patients aged 6 years or older, as well as those with generalized pustular psoriasis18. Earlier this year, Cosentyx was also approved in Brazil to treat ERA in patients 4 years or older and JPsA in patients aged 2 years and older19.
About the JUNIPERA trial
The positive CHMP opinion is based on data from the Phase III JUNIPERA study, a 2-year, three-part, double-blind, placebo-controlled, randomized withdrawal trial that enrolled 86 children and adolescents aged 2–18 years old with a confirmed diagnosis of ERA or JPsA according to a modified International League of Associations for Rheumatology classification criteria16. The primary endpoint of the study was time to flare in the treatment period 2 (Week 12 to Week 104)16. The study met its primary endpoint and demonstrated a statistically significant longer time to disease flare in treatment period 2 for ERA and JPsA with secukinumab versus placebo. The risk of flare was reduced by 72% for patients on secukinumab compared with patients on placebo in treatment period 2 (Hazard ratio=0.28, 95% CI: 0.13 to 0.63, p<0.001). A total of 21 patients in the placebo group experienced a flare event (11 JPsA and 10 ERA) compared with 10 patients in the secukinumab group (4 JPsA and 6 ERA) during the placebo-controlled treatment period 2 of the study8, 10. Safety in this pediatric population was consistent with the known safety profile of Cosentyx for the treatment of adult and pediatric plaque psoriasis, PsA and axial spondyloarthritis9.
About Cosentyx
Cosentyx is the first and only fully human biologic that directly inhibits interleukin-17A, an important cytokine involved in the inflammation of psoriatic arthritis (PsA), moderate to severe plaque psoriasis, ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)8, 20. Cosentyx is a proven medicine and has been studied clinically for more than 14 years. The medicine is backed by robust evidence, including 5 years of clinical data in adults supporting long-term safety and efficacy across moderate to severe plaque psoriasis, PsA and AS1-3, 5-7, 21. These data strengthen the position of Cosentyx as a treatment across AS, nr-axSpA, PsA and moderate to severe plaque psoriasis, supported by more than 700,000 patients treated worldwide since launch in 20158, 11, 22.
Find out more at https://www.novartis.com.
Novartis' Cosentyx gets EMA panel nod for expanded use in certain types of arthritis
May 20, 2022 9:37 AM ET Novartis AG (NVS)
By: Ravikash, SA News Editor
- A committee of the European Medicines Agency (EMA) recommended the approval for expanded use of Novartis' (NYSE:NVS) drug Cosentyx.
- https://seekingalpha.com/news/3841365-novartis-cosentyx-gets-ema-panel-nod-for-expanded-use-in-certain-types-of-arthritis
- https://seekingalpha.com/symbol/NVS
- https://www.cosentyx.com/
- https://www.novartis.com/
LUPKYNIS™
Aurinia Presents Results from the Two-Year AURORA 2 Continuation Study at the 2022 European Renal Association (ERA) Congress
DOWNLOAD AS PDF MAY 20, 2022
Use of LUPKYNIS was safe and well tolerated in patients for up to three years of treatment, with no new safety signals
In AURORA 2, long-term treatment with LUPKYNIS led to a clinically relevant preservation of kidney function in LN patients
A pooled analysis from the AURA-LV and AURORA 1 studies, also presented at ERA, showed early treatment response to LUPKYNIS with reductions in proteinuria across lupus nephritis biopsy classes
VICTORIA, British Columbia--(BUSINESS WIRE)-- Aurinia Pharmaceuticals Inc. (NASDAQ:AUPH) (Aurinia or the Company), a biopharmaceutical company committed to delivering therapeutics that change the course of autoimmune disease, today presented for the first time the results of the AURORA 2 continuation study evaluating the long-term safety and tolerability of LUPKYNIS™ (voclosporin) for the treatment of adults with active lupus nephritis (LN), a serious complication in patients with systemic lupus erythematosus (SLE). The results were presented during an oral session at the 59th European Renal Association (ERA) Congress, held in Paris and virtually May 19-22, 2022.
The AURORA 2 study assessed long-term safety and tolerability of voclosporin compared to placebo (both taken in combination with mycophenolate mofetil (MMF) and low-dose oral steroids) in patients with LN receiving treatment for an additional 24 months following completion of one year on treatment in the AURORA 1 study. The primary endpoint was safety and included assessments of adverse events, deaths, and hematological assessments. Secondary endpoints include renal response, renal flare, renal outcomes, and changes in urine protein to creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR).
“Lupus nephritis is a severe complication of lupus that will occur in up to half of patients diagnosed with SLE,” said Y.K. Onno Teng, M.D., Ph.D., Leiden University Medical Center, Leiden, The Netherlands, presenting author of the AURORA 2 ERA presentation and principal study investigator. “These results demonstrated that patients on long-term voclosporin therapy continue to experience clinically relevant benefits, including significant preservation of kidney function long-term, with no unexpected, new safety signals.”
Voclosporin was well tolerated during the study period with a similar safety profile to control and no unexpected safety signals. Specific findings included:
- Overall rates of serious adverse events were similar in both the control (28.0%) and voclosporin (26.0%) arms and there was no increase in infectious events.
- Generally adverse events were low and decreased over time on treatment.
- Significant and meaningful reductions in proteinuria achieved in AURORA 1 were maintained.
- In AURORA 2, there was a significant difference in eGFR slope in favor of voclosporin (-0.2 mL/min/1.73 m2) compared to control arm (-5.4 mL/min/1.73 m2).
- There was a small, expected, and early decrease in mean eGFR in the first four weeks of treatment in AURORA 1, after which eGFR remained stable through the end of AURORA 2.
- The mean UPCR was lower in the voclosporin-treated groups at all time points during the three years.
- There were four deaths in the active control group during AURORA 2, while none in the voclosporin-treated group.
“When treating patients with lupus nephritis, the ultimate goal is to preserve kidney function,'' said Neil Solomons, M.D., Chief Medical Officer at Aurinia. “We’re thrilled to build out the body of data that reinforces voclosporin as a safe and effective treatment option for lupus nephritis patients over the long term.”
A post-hoc analysis of pooled data from the AURA-LV and AURORA 1 studies was also presented during an oral session at the ERA Congress and examined the impact of voclosporin on the time to proteinuria reduction by biopsy class. The analysis reviewed pure class III, class IV, and class V biopsy groups and showed patients treated with voclosporin in addition to MMF and low dose steroids achieved earlier reductions in proteinuria across biopsy classes. These results support the efficacy results observed in the AURA-LV and AURORA 1 trials respectively, indicating a faster time to response when voclosporin is added to MMF and low-dose steroid treatment.
“The breadth of the AURORA clinical program provides important insights demonstrating the efficacy of voclosporin for the treatment of lupus nephritis across varying patient types," said Anca Askanase, M.D., M.P.H., Columbia University Medical Center and presenting author of the AURA-LV and AURORA 1 pooled analysis. "This analysis strengthens the clinical evidence supporting voclosporin as an important option that physicians can use in addition to the current standard of care treatment regimen to rapidly control lupus nephritis and protect kidney function.”
AURORA 2 Study Design
AURORA 2 (NCT03597464) is a Phase 3 randomized, double-blind, placebo-controlled clinical trial to assess the long-term safety and tolerability of voclosporin, in addition to MMF/steroids. Patients who completed 12 months of treatment in the Phase 3 AURORA 1 study were eligible to enroll in the AURORA 2 continuation study with the same randomized treatment of voclosporin at 23.7 mg twice daily or placebo, in combination with MMF at 1 g twice daily with low-dose oral steroids, for up to an additional 24 months. A total of 216 LN patients continued into AURORA 2, with 116 patients in the voclosporin-treated group and 100 patients in the active control group.
About AURORA 1
The AURORA 1 study was a 52-week study designed to evaluate the efficacy and safety of LUPKYNIS (23.7 mg twice daily) when added to background therapy of MMF and corticosteroids tapered to a low dose, compared to background therapy alone in an ethnically and racially diverse patient population with active LN. Three hundred fifty-seven patients with a diagnosis of SLE and LN according to the American College of Rheumatology criteria and a kidney biopsy within two years that showed Class III, IV and/or V LN were enrolled. AURORA 1 met its primary endpoint, achieving statistically superior complete renal response rates of 41% in the LUPKYNIS group versus 23% in the control group (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.64-4.27; p < 0.0001). LUPKYNIS also achieved statistical significance in all pre-specified hierarchical secondary endpoints, including reduced time to 50% reduction from baseline in UPCR and time to UPCR <0.5 mg/mg compared to control. The primary endpoint was complete renal response at 52 weeks defined as urine protein creatinine ratio (UPCR) ≤0.5 mg/mg, with stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for three or more consecutive days or for seven or more days during Weeks 44 through 52. LUPKYNIS was well tolerated with no unexpected safety signals. Serious adverse events (SAEs) were reported in 21% of those treated with LUPKYNIS and in 21% of those in the control group. Results from the completed AURORA 1 study (NCT03021499) were published in May 2021 in The Lancet.
About AURA-LV
The AURA–LV study (Aurinia Urinary protein Reduction in Active Lupus with Voclosporin) was a 48-week study comparing the efficacy of two doses of voclosporin added to current standard of care of MMF against standard of care with placebo in achieving CR in patients with active LN. All arms also received low doses of steroids as background therapy. 265 patients were enrolled at centers in 20 countries worldwide. On entry to the study, patients were required to have a diagnosis of LN according to established diagnostic criteria (American College of Rheumatology) and clinical and biopsy features indicative of highly active nephritis. The 24-week primary and secondary endpoints were released in Q3 2016 where the primary and all secondary endpoints were met. Complete remission (CR) is a composite endpoint that includes: confirmed UPCR of ≤0.5 mg/mg; normal, stable renal function (≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%); presence of sustained, low dose steroids (≤10mg prednisone from week 16-24); and no administration of rescue medications. Partial remission (PR) in the trial is measured by a ≥50% reduction in UPCR with no concomitant use of rescue medication.
About LUPKYNIS
LUPKYNIS™ is the first FDA-approved oral medicine for the treatment of adult patients with active LN. LUPKYNIS is a novel, structurally modified calcineurin inhibitor (CNI) with a dual mechanism of action, acting as an immunosuppressant through inhibition of T-cell activation and cytokine production and promoting podocyte stability in the kidney. The recommended starting dose of LUPKYNIS is three capsules twice daily with no requirement for serum drug monitoring. Dose modifications can be made based on Aurinia’s proprietary personalized eGFR-based dosing protocol. Boxed Warning, warnings and precautions for LUPKYNIS are consistent with those of other CNI-immunosuppressive treatments.
INDICATIONS
LUPKYNIS is indicated in combination with a background immunosuppressive therapy regimen for the treatment of adult patients with active LN. Limitations of Use: Safety and efficacy of LUPKYNIS have not been established in combination with cyclophosphamide. Use of LUPKYNIS is not recommended in this situation.
Please see Prescribing Information, including Boxed Warning, and Medication Guide for LUPKYNIS
View source version on businesswire.com: https://www.businesswire.com/news/home/20220520005341/en/
Source: Aurinia Pharmaceuticals Inc.
Released May 20, 2022
Aurinia Pharmaceuticals touts long-term benefit of Lupkynis for lupus
May 20, 2022 12:32 PM ET
Aurinia Pharmaceuticals Inc. (AUPH)
By: Jonathan Block, SA News Editor8 Comments
- Aurinia Pharmaceuticals (NASDAQ:AUPH) said that data from a study showed that its lupus nephritis treatment Lupkynis (voclosporin) led to preservation of kidney function over three years of treatment.
- https://seekingalpha.com/news/3841424-aurinia-pharmaceuticals-touts-long-term-benefit-of-lupkynis-for-lupus
- https://seekingalpha.com/symbol/AUPH
- https://www.lupkynis.com/
- https://www.auriniapharma.com/
XELJANZ- tofacitinib tablet, film coated
Xeljanz
Opinion
On 19 May 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Xeljanz prolonged-release tablets.1 The marketing authorisation holder for this medicinal product is Pfizer Europe MA EEIG.
The CHMP adopted a new indication for the treatment of ankylosing spondylitis. The full indications for Xeljanz prolonged-release tablets will therefore be as follows:2
Rheumatoid arthritis
Tofacitinib in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs (DMARDs) (see section 5.1). Tofacitinib can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate (see sections 4.4 and 4.5).
Psoriatic arthritis
Tofacitinib in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease modifying antirheumatic drug (DMARD) therapy (see section 5.1).
Ankylosing spondylitis
Tofacitinib is indicated for the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.
Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
EMA panel recommends Pfizer's Xeljanz for ankylosing spondylitis
May 20, 2022 9:59 AM ET
By: Jonathan Block, SA News Editor
- An advisory panel to the European Medicines Agency (EMA) is recommending approval of Pfizer's (NYSE:PFE) JAK inhibitor Xeljanz (tofacitinib) for ankylosing spondylitis.
- https://seekingalpha.com/symbol/PFE
- https://www.xeljanz.com/
biotecMAX™ Feb/Mar/APR/May 2022 Insight
OLUMIANT® (baricitinib)
CHMP Recommends Approval of Lilly and Incyte's OLUMIANT® (baricitinib) as the First and Only Centrally-Authorized Treatment for Adults with Severe Alopecia Areata (AA)
May 20, 2022Download PDF
INDIANAPOLIS, May 20, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ:INCY) announced today that the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for OLUMIANT® (baricitinib) for the treatment of adults with severe alopecia areata (AA).
This opinion marks the first step toward European regulatory approval of OLUMIANT for patients with severe AA, and it is now referred to the European Commission for final action. If approved, OLUMIANT would be the first centrally-authorized oral treatment and first JAK inhibitor for patients with severe AA in the European Union. The European Commission's decision is expected in the next one to two months.
"Alopecia areata is an often-misunderstood autoimmune disease that can lead to unpredictable hair loss, ranging from bald patches to complete loss of all hair. The disease carries significant psychosocial burden and can impact patients of any race, ethnicity, or age, with many experiencing alopecia in their early to mid-20s," said Bianca Maria Piraccini, M.D., Ph.D., professor and head of the Dermatology Unit at the University of Bologna. "As there has never been a centrally-authorized therapy for alopecia areata, I'm delighted about Lilly's potential to provide this oral medicine with statistically significant and clinically meaningful Phase 3 clinical trial results for adults with severe alopecia areata across Europe."
The positive opinion was based on Lilly's Phase 3 BRAVE-AA1 and BRAVE-AA2 trials evaluating the efficacy and safety of OLUMIANT in 1,200 patients with severe AA, the largest Phase 3 clinical trial program with completed primary endpoints. Severe AA was defined as having a Severity of Alopecia Tool (SALT) score ≥50 (≥50% scalp hair loss). The primary endpoint was the proportion of patients achieving SALT ≤20 (i.e., 80% or more scalp hair coverage) at Week 36. Across both studies, 1 out of 3 patients treated with OLUMIANT 4-mg achieved 80% or more scalp hair coverage (BRAVE-AA1=35.2% [n=99]; BRAVE-AA2=32.5% [n=76]), compared to 1 out of 20 patients (5.3%, n=10) and 1 out of 50 patients (2.6%, n=4) taking placebo in BRAVE-AA1 and BRAVE-AA2, respectively (p≤0.001 for all comparisons to placebo).
Achievement of full regrowth or regrowth with minimal gaps in eyebrow and eyelash hair was also seen at 36 weeks with OLUMIANT 4-mg for 1 in 3 patients who at baseline had significant gaps or no notable eyebrows or eyelashes, as compared to patients taking placebo (BRAVE-AA1: 4-mg dose: eyebrow=31.4% [n=59]; eyelash=33.5% [n=56]; placebo: eyebrow=3.2% [n=4]; eyelash=3.1% [n=3]; BRAVE-AA2: 4-mg dose: eyebrow=34.8% [n=56]; eyelash=34.3% [n=48]; placebo: eyebrow=4.5% [n=5]; eyelash=5.6% [n=5]; p≤0.001 for all comparisons to placebo). Eyebrow and eyelash hair loss was evaluated using the Clinician-Reported Outcome (ClinRO) Measure for Eyebrow Hair Loss™ and ClinRO Measure for Eyelash Hair Loss™ – novel, clinically-validated tools developed by Lilly.
The Phase 3 BRAVE-AA clinical program also evaluated the safety profile of OLUMIANT, and no new safety signals were observed. Few patients discontinued treatment due to adverse events (2.6% or less across both studies), and the majority of treatment-emergent adverse events were mild or moderate in severity.
"We're proud of today's CHMP opinion as it reflects our commitment to immunological diseases with high unmet need," said Patrik Jonsson, Lilly senior vice president, president of Lilly Immunology and Lilly USA, and chief customer officer. "This is a significant step for OLUMIANT on the path to becoming the first and only centrally-authorized medicine in Europe for adults with severe alopecia areata. We eagerly anticipate additional regulatory decisions around the world this year."
In February 2022, the U.S. Food and Drug Administration (FDA) granted priority review for OLUMIANT in adults with severe AA. Lilly expects additional regulatory decisions in the U.S. and Japan in 2022.
About OLUMIANT®
OLUMIANT, a once-daily, oral JAK inhibitor, was discovered by Incyte and licensed to Lilly. It is approved in the U.S. and more than 75 countries as a treatment for adults with moderate to severe rheumatoid arthritis and is approved in more than 50 countries, including the European Union and Japan, for the treatment of adult patients with moderate to severe atopic dermatitis who are candidates for systemic therapy. FDA approval was granted for OLUMIANT for the treatment of certain hospitalized adult patients with COVD-19 in May 2022. Marketing authorization for OLUMIANT in COVID-19 has been granted in six other countries including Japan and Switzerland. Baricitinib is authorized for emergency use in eight countries. Over 400,000 patients have been treated with OLUMIANT for approved indications, in addition to nearly one million patients with COVID-19 worldwide. The U.S. FDA-approved labeling for OLUMIANT includes a Boxed Warning for Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis. See the full Prescribing Information here. OLUMIANT is being investigated in alopecia areata (AA), juvenile idiopathic arthritis (JIA) and in pediatric patients with atopic dermatitis (AD).
In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of OLUMIANT and certain follow-on compounds for patients with inflammatory and autoimmune diseases.
Indications and Usage for OLUMIANT (baricitinib) tablets (in the United States)
OLUMIANT is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Limitations of Use: Not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (DMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.
OLUMIANT is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.
To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn.
About Incyte
Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.
OLUMIANT® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
View original content to download multimedia:https://www.prnewswire.com/news-releases/chmp-recommends-approval-of-lilly-and-incytes-olumiant-baricitinib-as-the-first-and-only-centrally-authorized-treatment-for-adults-with-severe-alopecia-areata-aa-301551999.html
SOURCE Eli Lilly and Company; Incyte
Lilly, Incyte's Olumiant get EMA panel nod for hair loss disorder alopecia areata
May 20, 2022 9:56 AM ET Incyte Corporation (INCY), LLY
By: Ravikash, SA News Editor
- A committee of the European Medicines Agency (EMA) recommended the approval of Eli Lilly (NYSE:LLY) and Incyte's (NASDAQ:INCY) Olumiant to treat adults with severe alopecia areata (AA).
- https://seekingalpha.com/news/3841375-lilly-incytes-olumiant-get-ema-panel-nod-for-hair-loss-disorder-alopecia-areata
- https://www.olumiant.com/
- https://seekingalpha.com/symbol/LLY
- https://seekingalpha.com/symbol/INCY
Sarclisa® (isatuximab)
PRESS RELEASES May 15 2022
Press Release: Sarclisa® (isatuximab) combination provides unprecedented median progression free survival in patients with relapsed multiple myeloma receiving a proteasome inhibitor therapy
Sarclisa® (isatuximab) combination provides unprecedented median progression free survival in patients with relapsed multiple myeloma receiving a proteasome inhibitor therapy
- Latest results of the Phase 3 IKEMA trial demonstrate the longest median progression free survival (mPFS) on a proteasome inhibitor backbone in patients who relapsed after a prior therapy, including lenalidomide
- The median progression free survival, increased from 19.2 months to 35.7 months when Sarclisa was added to carfilzomib and dexamethasone
- Further analysis, following U.S. Food and Drug Administration recommendations on censoring rules, showed mPFS increased from 20.8 to 41.7 months when Sarclisa was added to carfilzomib and dexamethasone
PARIS, May 15, 2022. Latest results from the Phase 3 IKEMA clinical trial evaluating Sarclisa® (isatuximab) in combination with carfilzomib and dexamethasone (Kd) demonstrated a median progression free survival (mPFS) of 35.7 months (Hazard Ratio HR 0.58; 95% Confidence Interval CI: 25.8 to 44.0; n=179), compared to 19.2 months in patients treated with Kd alone (95% CI: 15.8 to 25.1; n=123), as evaluated by an Independent Review Committee. These results, presented at the Controversies in Multiple Myeloma World Congress, represent the longest mPFS among studies investigating a proteasome inhibitor backbone in the second-line setting for the treatment of relapsed multiple myeloma (MM). These data will also be presented at the European Society for Medical Oncology on May 19.
Philippe Moreau, MD
Head of the Department of Hematology, University Hospital of Nantes, France
“The increase in progression free survival, observed consistently across all subgroups, when adding Sarclisa to carfilzomib and dexamethasone is remarkable in patients with relapsed multiple myeloma in a proteasome inhibitor combination. Relapse is common in multiple myeloma, creating the need for differentiated second-line treatments that provide patients a longer period of time without disease progression. This updated analysis reinforces the potential for Sarclisa to become a new standard of care for patients with relapsed multiple myeloma.”
A PFS analysis following the U.S. Food and Drug Administration recommendations on censoring rules, as applied in the approved U.S. prescribing information, showed an mPFS of 41.7 months for Sarclisa added to Kd (Sarclisa combination therapy) compared to 20.8 months in patients treated with Kd alone (HR 0.59; 95% CI: 27.1 to Not Calculable NC).
Time to next treatment for patients treated with Sarclisa combination therapy was 44.9 months (HR 0.55; 95% CI: 31.6 to NC) versus those treated with Kd alone at 25 months (95% CI: 17.9 to 31.3). Time to next treatment measured the interval from the date of randomization1 to the date of commencement of the next line of therapy, thereby allowing for measurement of the period of therapeutic benefit.2
Peter C. Adamson, MD
Global Head of Oncology Clinical Development and Pediatric Innovation at Sanofi
“To observe progression free survival of more than three years in patients with relapsed multiple myeloma when Sarclisa was added to a proteasome inhibitor backbone of therapy is unprecedented and reinforces our confidence in Sarclisa as a potential best in class anti-CD38 antibody.”
The safety and tolerability of Sarclisa observed in this analysis were consistent with the safety profile of Sarclisa in other clinical trials, with no new safety signals observed. For the Sarclisa combination therapy and Kd groups, the most common adverse events were infusion related reaction (45.8%, 3.3%), diarrhea (39.5%, 32%), hypertension (37.9%, 35.2%), upper respiratory tract infection (37.3%, 27%), fatigue (31.6%, 20.5%), dyspnoea (30.5%, 22.1%), pneumonia (27.1%, 21.3%), back pain (25.4%, 21.3%), insomnia (25.4%, 24.6%), and bronchitis (24.3%, 12.3%). Treatment exposure in the Sarclisa combination therapy arm was 30 weeks longer than in the control arm. Treatment emergent adverse events (TEAEs) of ≥ Grade 3 were reported in 83.6% of patients treated with Sarclisa combination therapy and in 73% of those treated with Kd alone. Serious TEAEs were higher in the Sarclisa combination therapy arm versus Kd alone (70.1% versus 59.8%). No difference was observed after exposure adjustment.”
These results will be discussed with regulatory authorities at a future date.
About the IKEMA trial
The randomized, multi-center, open label Phase 3 IKEMA clinical trial enrolled 302 patients with relapsed MM across 69 centers spanning 16 countries. All study participants had received one to three prior anti-myeloma therapies. During the trial, Sarclisa was administered through an intravenous infusion at a dose of 10mg/kg once weekly for four weeks, then every other week for 28-day cycles in combination with carfilzomib twice weekly at the 20/56mg/m2 dose and dexamethasone at the standard dose for the duration of treatment. The primary endpoint of IKEMA was progression free survival. Secondary endpoints included overall response rate, the rate of complete response or better, the rate of very good partial response or better, rate of minimal residual disease-negativity, overall survival and safety.3
About Sarclisa
Sarclisa is a monoclonal antibody that targets a specific epitope on the CD38 receptor on multiple myeloma (MM) cells. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.
Based on the Phase 3 ICARIA-MM study, Sarclisa is approved in a number of countries, including the U.S. and EU, in combination with pomalidomide and dexamethasone for the treatment of patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor. Based on the Phase 3 IKEMA study, Sarclisa is also approved in multiple countries in combination with carfilzomib and dexamethasone, including in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).
Sarclisa continues to be evaluated in multiple ongoing Phase 3 clinical trials in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies and solid tumors. The safety and efficacy of these additional uses have not been reviewed by any regulatory authority worldwide.
For more information on Sarclisa clinical trials, please visit www.clinicaltrials.gov.
Sanofi's Sarclisa combo reduces risk of multiple myeloma getting worse by ~3 years in study
May 16, 2022 6:12 AM ET Sanofi (SNY)
By: Ravikash, SA News Editor
Sanofi (NASDAQ:SNY) said new data from a late stage study of its multiple myeloma therapy Sarclisa, in combination with other drugs, showed reducing the risk of disease getting worse by a median of nearly three years.
https://seekingalpha.com/symbol/SNY
Verquvo™ (vericiguat)
Thursday - May 19, 2022
Not intended for U.S. and UK Media
Verquvo™ (vericiguat) approved in China to treat patients with chronic heart failure and reduced ejection fraction
Studied in adults with symptomatic chronic heart failure and reduced ejection fraction who are stabilized after a recent decompensation event with IV therapy / Approved in China to reduce the risk of heart failure (HF) hospitalization or the need for intravenous (IV) diuretics in emergency care / Approximately 13.7 million people in China live with heart failure(1)
Berlin, Germany, May 19, 2022 – Bayer announced today that China’s National Medical Products Administration (NMPA) has approved vericiguat under the brand name Verquvo™. Verquvo (2.5 mg, 5 mg, and 10 mg), a soluble guanylate cyclase (sGC) stimulator, is indicated in China to reduce the risk of heart failure (HF) hospitalization or requiring intravenous (IV) diuretics in emergency, in adults with symptomatic chronic HF and reduced ejection fraction (less than 45%) who are stabilized after a recent decompensation event with IV therapy. It works differently to existing heart failure treatments, providing a specific approach to managing chronic heart failure after a recent decompensation event with IV therapy, also known as a worsening heart failure event.1,2,3
“The approval of Verquvo is an important milestone for heart failure patients across China, providing a new option to help break the cycle of worsening heart failure events. Such events can lead to a downward spiral for many patients, resulting in repeated hospitalization,” said Dr. Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer. “With each hospital visit, the risk of death increases along with the emotional toll carried by patients and their families. For this reason, Bayer is proud to provide clinicians with access to Verquvo, to help improve outcomes and help alleviate the burden faced by patients living with chronic heart failure in China.”
Current therapies block the harmful effects of the natural neurohormonal systems that are activated by the myocardial and vascular dysfunction present in heart failure. Verquvo works through a different mode of action.2,4 It specifically restores the deficient NO-sGC-cGMP pathway, which plays a critical role in the progression of heart failure and aggravating its symptoms.4 Verquvo was studied and approved on top of standard-of-care.
Verquvo has been approved in the U.S, the EU, Japan, and many other countries worldwide. Multiple other submissions for marketing authorizations are ongoing worldwide.
Verquvo is being jointly developed with MSD (a tradename of Merck & Co., Inc., Kenilworth, NJ, USA).
About Verquvo™ (vericiguat)
Vericiguat 2.5 mg, 5 mg, and 10 mg is an oral once daily stimulator of soluble guanylate cyclase (sGC), an important enzyme in the nitric oxide (NO) signaling pathway.5 When NO binds to sGC, the enzyme catalyzes the synthesis of intracellular cyclic guanosine monophosphate (cGMP), a second messenger that plays a role in the regulation of vascular tone, cardiac contractility, and cardiac remodeling.5 Heart failure is associated with impaired synthesis of NO and decreased activity of sGC, which may contribute to myocardial and vascular dysfunction.5 By directly stimulating sGC, independently of and synergistically with NO, vericiguat augments levels of intracellular cGMP, leading to smooth muscle relaxation and vasodilation.4 In the EU Verquvo is indicated for symptomatic chronic heart failure in adult patients with reduced ejection fraction who are stabilized after a recent decompensation event requiring intravenous (IV) therapy.
About the Worldwide Collaboration between Bayer and MSD
Since October 2014, Bayer and MSD have pursued a worldwide collaboration in the field of sGC modulators. The collaboration brings together two leading companies that have stated their intent to fully evaluate this therapeutic class in areas of unmet medical need. The vericiguat program is being co-developed by Bayer and MSD. MSD has the commercial rights to vericiguat in the U.S. and Bayer has the exclusive commercial rights in the rest of world. The companies share equally the costs of the development of vericiguat.
R&D expenses before special items amounted to 5.3 billion euros. For more information, go to www.bayer.com.
Bayer, Merck's Verquvo gets approval in China to treat certain patients with heart failure
May 19, 2022 5:08 AM ET
Bayer Aktiengesellschaft (BAYRY), BAYZFMRK
By: Ravikash, SA News Editor
- China's National Medical Products Administration approved Bayer (OTCPK:BAYRY) (OTCPK:BAYZF) and Merck's (MRK) Verquvo to treat certain patients with heart failure (HF).
- https://seekingalpha.com/news/3840751-bayer-mercks-verquvo-gets-approval-in-china-to-treat-certain-patients-with-heart-failure
- https://seekingalpha.com/symbol/BAYRY
- https://seekingalpha.com/symbol/BAYZF
- https://seekingalpha.com/symbol/MRK
- https://www.verquvo-us.com/
- https://www.merck.com/
KEYTRUDA® (pembrolizumab)
Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) as Adjuvant Treatment for Adult and Adolescent (≥12 Years of Age) Patients With Stage IIB or IIC Melanoma Following Complete Resection
May 20, 2022 8:15 am ET
Opinion granted based on positive results from the Phase 3 KEYNOTE-716 trial
If approved, KEYTRUDA would be the first anti-PD-1 immunotherapy treatment option for patients 12 years and older in the EU across stage IIB, IIC and III melanoma following complete resection
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the adjuvant treatment of adults and adolescents aged 12 years and older with stage IIB or IIC melanoma and who have undergone complete resection. Additionally, the CHMP recommended expanding the indications for KEYTRUDA in advanced (unresectable or metastatic) melanoma and stage III melanoma (as adjuvant treatment following complete resection) to include adolescent patients aged 12 years and older.
“Based on the results of the KEYNOTE-716 trial, KEYTRUDA has shown a significant improvement in recurrence-free survival and distant metastasis-free survival for these patients with resected stage IIB or IIC melanoma,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “The CHMP’s positive recommendation brings us one step closer to providing patients 12 years and older in the European Union with a new option for resected stage IIB or IIC melanoma that can reduce the risk of their cancer returning.”
The positive opinion was granted based on results from the Phase 3 KEYNOTE-716 trial, which demonstrated a statistically significant improvement in recurrence-free survival with KEYTRUDA compared to placebo (HR=0.65 [95% CI, 0.46-0.92]; p=0. 0.00658) in patients 12 years and older with stage IIB and IIC melanoma following complete resection. Earlier this year, Merck reported that KEYNOTE-716 also met its key secondary endpoint of distant metastasis-free survival. These results will be featured in a late-breaking oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting on June 5 (Abstract #LBA9500).
The CHMP’s recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second or third quarter of 2022.
About Merck’s research in melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases of melanoma diagnosed worldwide in 2020, and melanoma is the leading cause of skin cancer deaths, with more than 57,000 deaths from the disease worldwide in 2020. In Europe, it is estimated there were more than 150,000 new cases of melanoma diagnosed and more than 26,000 deaths from the disease in 2020.
The recurrence rates for resected melanoma are estimated to be 32-46% for patients with stage IIB and IIC disease and 39-74% for patients with stage III disease. The five-year survival rates are estimated to be 87% for stage IIB, 82% for stage IIC, 93% for stage IIIA, 83% for stage IIIB, 69% for stage IIIC and 32% for stage IIID.
Merck is committed to delivering meaningful advances for patients with melanoma with KEYTRUDA and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of adult patients with resected stage III melanoma and is approved in over 90 countries based on the results from EORTC1325/KEYNOTE-054. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.
Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids were required in 69% (33/48); additional immunosuppressant therapy was required in 4.2% of patients. Colitis led to permanent discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Colitis resolved in 85% of the 48 patients.
Hepatotoxicity and Immune-Mediated Hepatitis
KEYTRUDA as a Single Agent
KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 68% (13/19) of patients; additional immunosuppressant therapy was required in 11% of patients. Hepatitis led to permanent discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Hepatitis resolved in 79% of the 19 patients.
KEYTRUDA With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids were required in 77% (17/22) of patients; of these, the majority remained on systemic corticosteroids. Adrenal insufficiency led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.
Hypophysitis
KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids were required in 94% (16/17) of patients; of these, the majority remained on systemic corticosteroids. Hypophysitis led to permanent discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.
Thyroid Disorders
KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in <0.1% (1) of patients.
Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. Hypothyroidism occurred in 8% (237/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (6.2%). It led to permanent discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement. The majority of patients with hypothyroidism required long-term thyroid hormone replacement. The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC, occurring in 16% of patients receiving KEYTRUDA as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. The incidence of new or worsening hypothyroidism was higher in 389 adult patients with cHL (17%) receiving KEYTRUDA as a single agent, including Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.
Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement.
Immune-Mediated Nephritis With Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 89% (8/9) of patients. Nephritis led to permanent discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, none had recurrence. Nephritis resolved in 56% of the 9 patients.
Immune-Mediated Dermatologic Adverse Reactions
KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti–PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received KEYTRUDA or were reported with the use of other anti–PD-1/PD-L1 treatments. Severe or fatal cases have been reported for some of these adverse reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
Source: Merck & Co., Inc.
Merck's blockbuster Keytruda gets EMA panel nod for expanded use in skin cancer
May 20, 2022 9:20 AM ET
By: Ravikash, SA News Editor
A committee of the European Medicines Agency (EMA) recommended the approval for expanded use of Merck's (NYSE:MRK) blockbuster drug Keytruda in certain patients with a type of skin cancer called melanoma.
https://seekingalpha.com/symbol/MRK
OXLUMO™ (lumasiran)
Alnylam Announces Health Canada Authorization of OXLUMO™ (lumasiran), the First and Only Treatment for Primary Hyperoxaluria Type 1 to Lower Urinary Oxalate Levels in Paediatric and Adult Patients
May 18, 2022 8:00 AM ET
Alnylam Pharmaceuticals, Inc. (ALNY)
Authorization Based on two Pivotal Phase III trials, ILLUMINATE-A and ILLUMINATE-B; Showing Significant Reduction in Urinary Oxalate which Drives the Progression of PH1 Disease
TORONTO, May 18, 2022 /CNW/ - Alnylam Pharmaceuticals, Inc. (ALNY) (Nasdaq: ALNY) is pleased to announce that Health Canada has issued a Notice of Compliance (NOC) authorizing OXLUMO™ (lumasiran) injection for subcutaneous use for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in paediatric and adult patients.1
PH1 is an ultra-rare and debilitating genetic disease of the liver characterized by oxalate overproduction.2 Oxalate is an end-product of metabolism and high levels of it are toxic because it cannot be broken down by the human body. Oxalate overproduction results in the deposition of calcium oxalate crystals in the kidneys and urinary tract and can lead to the formation of painful and recurrent kidney stones, nephrocalcinosis (renal deposition of calcium oxalate crystals), progression to ESKD (kidney failure), and systemic organ dysfunction.3
There are several types of primary hyperoxaluria (PH), however, PH1 is the most common and the most severe form accounting for 70 to 80 per cent of all PH cases.4 PH1 affects approximately four individuals per million with some regions, such as the Middle East and North Africa having a higher genetic prevalence.5 Symptom onset ranges from early infancy to sixty years of age with the median age being four to six years.6 The remainder of affected cases present in adulthood with 20 to 50 per cent presenting late stages of chronic kidney disease when diagnosed.7
Until today, there were no authorized pharmaceutical therapies for PH1. The only curative treatment is a liver transplant and if the patient has already progressed to kidney failure, then a dual liver/kidney transplant is required. Unfortunately, liver transplantation is associated with high morbidity and mortality, and life-long immunosuppression, leaving patients with limited options.
"PH1 is a challenging condition to diagnose and treat due to significant variations in the age of onset, rate of disease progression, and associated clinical manifestations," says Dr. Elizabeth Harvey, Pediatric Nephrologist, The Hospital for Sick Children (SickKids), Associate Professor Pediatrics, University of Toronto and member of Alnylam Canada's Scientific Advisory Board. "The approval of this therapy presents patients with a novel treatment option that may potentially reduce the oxalate burden responsible for causing their disease."
OXLUMO™ was granted NOC based on the results of a randomized, double-blind, placebo-controlled clinical study in patients six years and older with PH1 (ILLUMINATE-A) and in a single-arm clinical study in patients less than 6 years of age with PH1 (ILLUMINATE-B).8 The ILLUMINATE-A study showed that OXLUMO™ met its primary endpoint, evidenced by a 53 per cent mean reduction in urinary oxalate, and a 65 per cent mean reduction in urinary oxalate relative to baseline.9 In ILLUMINATE-B, OXLUMO™ demonstrated a 72 per cent mean reduction in spot urinary oxalate:creatinine ratio from baseline to month six (averaged from months three to six), meeting its primary endpoint.10
"This milestone is exciting, as it represents the third RNAi treatment to be brought to Canada in 3 years to treat rare and ultra-rare diseases," says Colleen Coxson, Country General Manager, Canada, Alnylam Pharmaceuticals. "Unfortunately for many patients, it can often take years to diagnose a rare disease, and just as long to find a treatment. Bringing Oxlumo to Canadian patients with PH1 further cements Alnylam Canada's commitment to the rare disease community."
OXLUMO™ is a double-stranded siRNA that reduces the levels of the enzyme glycolate oxidase (GO) responsible for supporting the production of oxalate by targeting the hydroxy acid oxidase 1 (HAO1) messenger ribonucleic acid (mRNA) in major cells of the liver known as hepatocytes through RNA interference. As a result, decreased GO enzyme levels reduce the amount of urinary and plasma oxalate levels, the underlying cause of disease manifestations in patients with PH1.11
"Previously there have been no authorized treatment options for PH1 in Canada, so this is a potentially life-changing milestone for people diagnosed with this debilitating disease – many of whom are infants and children. OXLUMO™ represents an exciting new frontier for the treatment of patients with this serious genetic disease," says Dr. Kristopher Garlick, Country Medical Director, Canada, Alnylam Pharmaceuticals.
About OXLUMO™ (lumasiran)
OXLUMOTM is a double-stranded iRNA therapeutic that reduces the levels of the enzyme glycolate oxidase (GO) by targeting the hydroxyacid oxidase 1 (HAO1) messenger ribonucleic acid (mRNA) in hepatocytes through RNA interference. Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in patients with PH1. As the GO enzyme is upstream of the alanine:glyoxylate aminotransferase (AGT) enzyme, the deficiency of which causes PH1, the mechanism of action of lumasiran is independent of the underlying AGXT gene mutation encoding AGT.12 In the ILLUMINATE-A study, OXLUMOTM was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. Injection site reactions (ISRs) were the most common drug-related adverse reaction.13 In the ILLUMINATE-B study, OXLUMOTM demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A.14 OXLUMOTM is administered via subcutaneous injection once monthly for three months, then once quarterly thereafter at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMOTM should be administered by a healthcare professional.15
SOURCE Alnylam Pharmaceuticals, Inc.
Alnylam's Oxlumo gets Health Canada nod for rare kidney disorder
May 18, 2022 8:30 AM ET
Alnylam Pharmaceuticals, Inc. (ALNY)
By: Ravikash, SA News Editor
- Alnylam Pharmaceuticals (NASDAQ:ALNY) said Health Canada issued a notice of compliance (NOC) authorizing its Oxlumo (lumasiran) injection for subcutaneous use as a therapy for primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in children and adult patients.
- https://seekingalpha.com/news/3840385-alnylams-oxlumo-gets-health-canada-nod-for-rare-kidney-disorder
- https://seekingalpha.com/symbol/ALNY
- https://www.alnylam.com/
- https://www.oxlumo.com/
PT027, a novel fixed-dose combination of albuterol and budesonide
PT027, a novel fixed-dose combination of albuterol and budesonide, used as an as-needed rescue medicine, significantly reduced the risk of a severe exacerbation compared to albuterol by 27% in patients with asthma
PUBLISHED15 May 2022
15 May 2022 17:30 BST
First time an albuterol/budesonide fixed-dose combination rescue medication has been shown to reduce severe exacerbations
MANDALA Phase III trial results published in the New England Journal of Medicine and presented at ATS 2022 International Conference
Full results from the positive MANDALA Phase III trial showed that PT027 (albuterol/budesonide) at two different strengths of budesonide, an inhaled corticosteroid (ICS), used as an as-needed rescue medicine, demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma.1,2
PT027 is a potential first-in-class inhaled, fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agonist (SABA), and budesonide in the US. It is being developed by AstraZeneca and Avillion.
Globally, more than 176 million asthma attacks are experienced each year.3
Compared with albuterol rescue, PT027 at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p<0.001) in adults and adolescents.1,2 In the trial, patients were randomised to receive PT027 or albuterol rescue, on top of their usually prescribed maintenance ICS, with or without additional controller medicines.1,2
In secondary endpoints, PT027 (180mcg albuterol/160mcg budesonide) demonstrated a 33% reduction in mean annualised total systemic corticosteroid exposure (p=0.002) and a 24% reduction in annualised severe exacerbation rate (p=0.008).1,2 A numerically higher odds of patients experiencing an improvement in symptom control and quality of life was also observed after 24 weeks of treatment with PT027 compared to albuterol rescue.1,2
Adverse events (AEs) were similar across the treatment groups in the trial and consistent with the known safety profiles of the individual components, with the most common AEs including nasopharyngitis and headache.1
Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of Capital Allergy & Respiratory Disease Center in Sacramento, US, said:
“The MANDALA Phase III trial results demonstrated that PT027, a novel fixed-dose combination of albuterol/budesonide used as-needed, provided additional anti-inflammatory treatment in response to patient symptoms, which led to a reduced risk of severe exacerbations compared with albuterol alone. These data further strengthen the growing body of evidence around the value of as-needed anti-inflammatory treatment in asthma and support PT027’s potential to transform the current rescue treatment approach.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Asthma is an inflammatory, variable disease and patients are at risk of experiencing a severe exacerbation regardless of disease severity and adherence to treatment. The results from these Phase III trials support the clinical benefit of PT027, an albuterol/budesonide rescue inhaler, which has the potential to be a first-in-class treatment approach that can prevent asthma attacks over and above their current maintenance therapies.”
In the MANDALA trial, PT027 at a lower budesonide dose (180mcg albuterol/80mcg budesonide), also demonstrated a statistically significant reduction of 17% in the risk of severe exacerbation versus albuterol rescue (p=0.041), when used as an as-needed rescue medicine in adults, adolescents, and children aged 4–11 years.1,2
The results were published in the New England Journal of Medicine and will be presented at the American Thoracic Society (ATS) 2022 International Conference.1,2,4
Also being presented at the ATS International Conference this week are the positive DENALI Phase III trial results. In this trial, PT027 demonstrated a statistically significant improvement in lung function measured by forced expiratory volume in one second (FEV1), compared to the individual components albuterol and budesonide, and compared to placebo in patients with mild to moderate asthma aged 12 years or older. Onset of action and duration of effect were similar for PT027 and albuterol. The safety and tolerability of PT027 in DENALI was consistent with the known profiles of the components.5
MANDALA
MANDALA1,19 was a Phase III, randomised, double-blind, multicentre, parallel-group, event-driven trial evaluating the efficacy and safety of PT027 compared to albuterol on the time to first severe asthma exacerbation in 3,132 adults, adolescents, and children (aged 4–11 years) with moderate to severe asthma taking ICS alone or in combination with a range of asthma maintenance therapies, including long-acting beta2-agonists (LABA), leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA) or theophylline. The trial comprised a two-to-four-week screening period, at least a 24-week treatment period and a two-week post-treatment follow-up period.
Patients were randomly assigned to one of the following three treatment groups in a 1:1:1 ratio: PT027 180/160mcg (excluding children aged 4–11 years), PT027 180/80mcg or albuterol 180mcg, taken as an as-needed rescue medicine. PT027 and the albuterol comparator were delivered in a pressurised metered-dose inhaler (pMDI) using AstraZeneca’s Aerosphere delivery technology. The primary efficacy endpoint was the time to first severe asthma exacerbation during the treatment period. Secondary endpoints included severe exacerbation rate (annualised), total systemic corticosteroid exposure (annualised), asthma control and health-related quality of life.
DENALI
DENALI4,20,21 was a Phase III, randomised, double-blind, placebo-controlled, multicentre, parallel-group trial evaluating the efficacy and safety of PT027 compared to its components albuterol and budesonide on improvement in lung function in 1,001 adults, adolescents, and children aged 4–11 years with mild to moderate asthma previously treated either with SABA as-needed alone or in addition to regular low-dose ICS maintenance therapy. The trial comprised a two-to-four-week screening period, a 12-week treatment period and a two-week post-treatment follow-up period.
Patients were randomly assigned to one of the following five treatment groups in a 1:1:1:1:1 ratio: PT027 180/160mcg four times daily (excluding children aged 4–11 years), PT027 180/80mcg four times daily, albuterol 180mcg four times daily, budesonide 160mcg four times daily (excluding children aged 4–11 years) and placebo four times daily. PT027, the albuterol and budesonide comparators and placebo were delivered in a pMDI using AstraZeneca’s Aerosphere delivery technology. The dual primary efficacy endpoints were change from baseline in FEV1 area under the curve 0-6 hours over 12 weeks of PT027 compared to budesonide to assess the effect of albuterol and change from baseline in trough FEV1 at Week 12 of PT027 compared to albuterol to assess the effect of budesonide. Secondary endpoints included the time to onset and duration of response on day one, number of patients who achieved a clinically meaningful improvement in asthma control from baseline at Week 12 and trough FEV1 at Week 1.
PT027
PT027 is a potential first-in-class SABA/ICS rescue treatment for asthma in the US, to be taken as needed. It is an inhaled, fixed-dose combination rescue medication containing albuterol (also known as salbutamol), a SABA, and budesonide, a corticosteroid, and is being developed in a pMDI using AstraZeneca’s Aerosphere delivery technology.
AstraZeneca and Avillion collaboration
In March 2018, AstraZeneca and Avillion signed an agreement to advance PT027 through a global clinical development programme for the treatment of asthma. Under the terms of the agreement, Avillion became the trial sponsor responsible for executing and funding the multicentre, global clinical trial programme for PT027 through NDA filing to a regulatory decision in the US. Following the successful approval of PT027, AstraZeneca has the option, upon certain financial payments, to commercialise the medicine in the US.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Avillion's asthma inhaler therapy PT027 reduces exacerbations in phase 3 trial
May 16, 2022 6:45 AM ET
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) said full results from a late stage study of its inhaled asthma therapy PT027 showed that the rescue medication helped reduce severe exacerbations by 27%.
https://seekingalpha.com/symbol/AZN
OLUMIANT® (baricitinib)
FDA Approves Lilly and Incyte's OLUMIANT® (baricitinib) for the Treatment of Certain Hospitalized Patients with COVID-19
May 11, 2022Download PDF
OLUMIANT is the first and only JAK inhibitor FDA-approved for the treatment of COVID-19 in certain hospitalized adults requiring various degrees of oxygen support
INDIANAPOLIS, May 11, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) and Incyte (NASDAQ: INCY) announced today the U.S. Food and Drug Administration (FDA) has approved OLUMIANT® (baricitinib) for the treatment of COVID-19 in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO) with a recommended dose of 4-mg once daily for 14 days or until hospital discharge, whichever comes first.
"More than two years into the pandemic, COVID-19 is still hospitalizing many people and burdening our healthcare system. I'm grateful to have OLUMIANT as a treatment option for those who require various degrees of respiratory support, from supplemental oxygen to mechanical ventilation or ECMO," said Andre Kalil, M.D., M.P.H., Professor of Medicine at the University of Nebraska Medical Center and principal investigator of the Adaptive COVID-19 Treatment Trial 2 (ACTT-2) sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). "I'm encouraged by the FDA's full approval of OLUMIANT for the treatment of these patients based on results from the rigorous, placebo-controlled, double-blind, randomized trials. While there are therapies currently available, there is still an urgent need for more options to help improve outcomes for patients hospitalized due to COVID-19."
The FDA's approval is supported by results from two randomized, double-blind, placebo-controlled Phase 3 studies (ACTT-2 and COV-BARRIER, including the COV-BARRIER OS 7 addendum study), announced previously. No new safety signals potentially related to the use of OLUMIANT were identified in the studies.
"Nearly one million people with COVID-19 have been treated with OLUMIANT (baricitinib) in approximately 15 countries worldwide," said Patrik Jonsson, Lilly senior vice president, president of Lilly Immunology and Lilly USA, and chief customer officer. "Today's full approval reflects both our confidence in OLUMIANT's role in treating these hospitalized patients and Lilly's tireless efforts to support the medical community and patients in the ongoing fight against COVID-19."
Baricitinib has been available in the U.S. under Emergency Use Authorization (EUA) since November 2020. An EUA will remain in place for hospitalized pediatric patients 2 to less than 18 years old who require various degrees of oxygen support. The emergency authorization is not an approval and is temporary for the duration where circumstances justify the authorization. For additional information about the authorized use, please see the FDA Letter of Authorization, Fact Sheet for Healthcare Providers and Fact Sheet for Patients, Parents and Caregivers.
Lilly has submitted applications for regulatory approval or authorization to multiple regulatory agencies around the world and anticipates further regulatory decisions to follow.
The U.S. FDA-approved labeling for OLUMIANT carries a boxed warning for risk of serious infections, mortality, malignancy, major adverse cardiovascular events (MACE) and thrombosis. Patients treated with OLUMIANT are at an increased risk of serious bacterial, fungal, viral and opportunistic infections leading to hospitalization or death, including tuberculosis. Higher rates of all-cause mortality and MACE have been observed with another JAK inhibitor versus tumor necrosis factor (TNF) blockers. Malignancies and thrombosis have occurred in patients treated with OLUMIANT and higher rates of each have been observed with another JAK inhibitor versus TNF blockers. Consider the risks and benefits of treatment prior to initiating or continuing therapy with OLUMIANT. Please see additional Important Safety Information below.
OLUMIANT is a once-daily, oral JAK inhibitor discovered by Incyte and licensed to Lilly. To learn more about OLUMIANT, please visit www.OLUMIANT.com. OLUMIANT is available in the U.S. as 1-mg and 2-mg tablets through Lilly's authorized specialty distributors.
About ACTT-2 (COVID I) Study
ACTT-2 was a randomized, double-blind, placebo-controlled clinical trial of certain hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with OLUMIANT and remdesivir (combination group; n=515) to treatment with placebo and remdesivir (placebo group; n=518). Patients treated with the combination received OLUMIANT 4-mg once daily (orally) for 14 days or until hospital discharge, whichever was first, and remdesivir 200-mg on Day 1 and 100-mg once-daily (via intravenous infusion) on subsequent days for a total treatment duration of 10 days or until hospital discharge, whichever was first.
The primary endpoint, for the intent to treat population, was time to recovery within 29 days after randomization. Recovery was defined as being discharged from the hospital without limitations on activities, being discharged from the hospital with limitations on activities and/or requiring home oxygen, or hospitalized but not requiring supplemental oxygen and no longer requiring medical care. The key secondary endpoint was clinical status on Day 15, as assessed on an 8-point ordinal scale.
About COV-BARRIER (COVID II) Study
COV-BARRIER was a randomized, double-blind, placebo-controlled clinical trial of certain hospitalized adults with confirmed SARS-CoV-2 infection that compared treatment with OLUMIANT 4-mg once daily (n=764) with placebo (n=761). OLUMIANT was administered for 14 days or until hospital discharge, whichever came first. Patients could remain on background standard of care, as defined per local guidelines.
Patients requiring invasive mechanical ventilation or ECMO at baseline were enrolled in an exploratory addendum study of COV-BARRIER. These patients were not included in the main COV-BARRIER study population and were analyzed separately.
The primary endpoint was the proportion of patients who died or progressed to non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation within the first 28 days of the study. Patients who required non-invasive ventilation/high-flow oxygen at baseline needed to worsen by at least 1 point on an 8-point ordinal scale to progress. A key secondary endpoint was all-cause mortality by Day 28.
About COV-BARRIER OS 7 Addendum Study
The COV-BARRIER OS 7 addendum study was an exploratory, randomized, double-blind, placebo-controlled substudy of COV-BARRIER in certain hospitalized adults with confirmed SARS-CoV-2 infection requiring invasive mechanical ventilation or ECMO at baseline. This substudy compared treatment with OLUMIANT 4-mg once daily + standard of care (SOC) (n=51) with placebo + SOC (n=50). All patients received SOC in keeping with local clinical practice for COVID-19 management. OLUMIANT was administered for 14 days or until hospital discharge, whichever occurred first. All endpoints in this substudy are considered exploratory, including the prespecified endpoint of all-cause mortality by Day 28.
Indication and Usage for OLUMIANT (baricitinib) tablets (in the United States)
OLUMIANT is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).
Please click to access full Prescribing Information, including Boxed Warning about Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis, and Medication Guide.
BA HCP ISI COV 11MAY2022
About OLUMIANT®
OLUMIANT, a once-daily, oral JAK inhibitor, was discovered by Incyte and licensed to Lilly. It is approved in the U.S. and more than 75 countries as a treatment for adults with moderate to severe rheumatoid arthritis. Marketing authorization for the treatment of hospitalized patients with COVID-19 and approval has been granted for OLUMIANT in multiple countries. To date, nearly one million patients worldwide with COVID-19 have been treated with OLUMIANT (baricitinib). The U.S. FDA-approved labeling for OLUMIANT includes a Boxed Warning for Serious Infections, Mortality, Malignancy, Major Adverse Cardiovascular Events, and Thrombosis. See the full Prescribing Information here.
In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of OLUMIANT and certain follow-on compounds for patients with inflammatory and autoimmune diseases.
To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY
For additional information on Incyte, please visit Incyte.com and follow @Incyte.
OLUMIANT® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
View original content to download multimedia:https://www.prnewswire.com/news-releases/fda-approves-lilly-and-incytes-olumiant-baricitinib-for-the-treatment-of-certain-hospitalized-patients-with-covid-19-301544527.html
SOURCE Eli Lilly and Company
Lilly, Incyte get FDA approval of Olumiant to treat certain hospitalized COVID-19 patients
May 11, 2022 7:16 AM ET
Eli Lilly and Company (LLY), INCY
By: Ravikash, SA News Editor
The U.S. Food and Drug Administration (FDA) approved Eli Lilly (NYSE:LLY) and Incyte's (NASDAQ:INCY) JAK inhibitor medicine Olumiant (baricitinib) to treat certain patients with COVID-19.
https://seekingalpha.com/symbol/INCY
https://seekingalpha.com/symbol/LLY
Upadacitinib (RINVOQ®)
May 11, 2022
Upadacitinib (RINVOQ®) Achieved Clinical Remission and Endoscopic Response at One Year in Phase 3 Maintenance Study in Patients with Crohn's Disease
- In patients with moderate to severe Crohn's disease who achieved clinical response to upadacitinib induction treatment, a significantly greater proportion treated with either 15 mg or 30 mg of upadacitinib achieved clinical remission,a,b endoscopic responsec and endoscopic remissiond at week 52 compared to placebo
- The safety results in this study were generally consistent with the known profile of upadacitinib, with no new safety risks observed
- Upadacitinib, a JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy for moderate to severe Crohn's disease and several other immune-mediated diseases
NORTH CHICAGO, Ill., May 11, 2022 /PRNewswire/ -- AbbVie today announced positive topline results from U-ENDURE, its Phase 3 maintenance study evaluating upadacitinib in adult patients with moderate to severe Crohn's disease who had an inadequate response or were intolerant to a conventional or biologic therapy. The results showed that more patients treated with either dose of upadacitinib (15 mg or 30 mg once daily) achieved the co-primary endpoints of endoscopic response and clinical remission, as well as the secondary endpoint of endoscopic remission, at one year (week 52) compared to placebo.1 Use of upadacitinib in Crohn's disease has not been evaluated by health authorities. Results from the U-ENDURE maintenance study, in addition to results from the U-EXCEED and U-EXCEL induction studies, will be included in future regulatory submissions.
In the U-ENDURE maintenance study, patients from U-EXCEED and U-EXCEL who responded to 12 weeks of upadacitinib 45 mg oral induction treatment were re-randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo. Clinical remission was defined by the Crohn's Disease Activity Index (CDAI) or by stool frequency and abdominal pain score (SF/AP).
A significantly higher proportion of patients who received upadacitinib 15 mg or 30 mg achieved clinical remission per the CDAI at week 52: 37 and 48 percent, respectively, versus 15 percent in the placebo group (p<0.0001).1 Results also showed that 36 and 46 percent of patients who received upadacitinib 15 mg and 30 mg, respectively, achieved clinical remission at week 52 per SF/AP compared to 14 percent in the placebo group (p<0.0001).1 At week 52, 28 and 40 percent of patients who received upadacitinib 15 mg and 30 mg, respectively, achieved endoscopic response compared to 7 percent of patients who received placebo (p<0.0001).1 In addition, 19 and 29 percent of patients who received upadacitinib 15 mg and 30 mg achieved endoscopic remission, respectively, compared to 5 percent of patients in the placebo group (p<0.0001).1 A significantly higher proportion of patients who received upadacitinib 15 mg or 30 mg achieved corticosteroid-free clinical remission per CDAI and per SF/AP compared to placebo at week 52 among patients taking corticosteroids at baseline.1
"We are deeply committed to supporting Crohn's disease patients who continue to live with challenging symptoms that impact their daily lives," said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. "These results represent important progress as we work to bring new treatment options to patients with inflammatory bowel disease."
"Symptomatic relief as well as healing of the intestinal mucosa in Crohn's disease are important long-term treatment targets which may be associated with slowing disease progression and better quality of life for patients," said Julian Panes, Emeritus Professor of Medicine and the Chief of the IBD Unit at Hospital Clínic de Barcelona and lead study investigator. "These results are encouraging and would be particularly important for patients who have not found relief with other conventional or biologic treatment options."
About U-ENDURE
The U-ENDURE study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled maintenance and long-term study designed to evaluate the efficacy and safety of upadacitinib 15 mg and 30 mg in adults with moderate to severe Crohn's disease. U-ENDURE enrolled patients who responded to 12 weeks of induction treatment from the U-EXCEED and U-EXCEL studies. In addition to the double-blind, placebo-controlled component, the U-ENDURE study also included patients from the induction studies who either responded to placebo or to extended treatment (an additional 12 weeks with 30 mg upadacitinib). During the study, patients who lost response were eligible to receive 30 mg upadacitinib as rescue therapy.
The study included slightly different sets of primary and secondary endpoints for the U.S. Food and Drug Administration (FDA) and the EU European Medicines Agency (EMA). The primary endpoints were achievement of clinical remission (per CDAI for the U.S. FDA, and per SF/AP for the EU EMA, which was measured by average daily very soft or liquid stool frequency and abdominal pain score) and endoscopic response (per SES-CD) at week 52. More information can be found on www.clinicaltrials.gov (NCT03345823).
About the Upadacitinib Phase 3 Crohn's Disease Program4,5,6
The global upadacitinib Phase 3 program evaluates more than 1,000 patients with moderate to severe Crohn's disease across two induction studies and a maintenance study. These studies include assessments of efficacy, safety and tolerability of upadacitinib. More information on these trials can be found at www.clinicaltrials.gov (NCT03345836, NCT03345849, NCT03345823).
About Upadacitinib (RINVOQ®)
Discovered and developed by AbbVie scientists, RINVOQ is a JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.7-14 Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK1 vs JAK2, JAK3, and TYK2.14 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.
Phase 3 trials of RINVOQ in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative colitis, giant cell arteritis, Takayasu arteritis and vitiligo are ongoing.7-14 The use of upadacitinib in Crohn's disease is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
RINVOQ® (upadacitinib) U.S. Use and Important Safety Information14
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with active psoriatic arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
- Adults with active ankylosing spondylitis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, or ankylosing spondylitis.
- Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) that did not respond to previous treatment and whose eczema is not well controlled with other pills or injections, including biologic medicines, or when the use of other pills or injections is not recommended.
RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.
It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.
For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
AbbVie's Rinvoq demonstrates remission at one year in Crohn's patients
May 11, 2022 9:58 AM ET
By: Jonathan Block, SA News Editor2 Comments
- Topline data from a phase 3 trial showed that more Crohn's disease patients treated with AbbVie's (NYSE:ABBV) Rinvoq (upadacitinib) achieved clinical and endoscopic remission after one year compared to those on placebo.
- https://seekingalpha.com/news/3836825-abbvie-rinvoq-demonstrates-remission-at-one-year-in-crohns-patients
- https://seekingalpha.com/symbol/ABBV
- https://www.rinvoq.com/
- https://www.abbvie.com/
Onyx Frontier™ drug-eluting stent
MAY 13, 2022
Medtronic receives FDA approval for latest generation drug-eluting coronary stent system
The Onyx Frontier™ drug-eluting stent offers an innovative delivery system and builds upon the acute performance and clinical data from the Resolute Onyx™ drug-eluting stent
DUBLIN, May 13, 2022 /PRNewswire(opens new window)/ -- Medtronic plc (NYSE:MDT), a global leader in healthcare technology, today announced it received U.S. Food and Drug Administration (FDA) approval for the Onyx Frontier™ drug-eluting stent (DES). As the latest evolution in the Resolute DES family, Onyx Frontier DES leverages the same best-in-class stent platform as Resolute Onyx™ DES, with an enhanced delivery system1 designed to improve deliverability and increase acute performance2 in even the most challenging of cases.1
The Onyx Frontier DES is used for the treatment of patients with coronary artery disease (CAD), which is caused by plaque buildup on the inside of the coronary arteries. These plaque deposits can narrow or clog the inside of the arteries, which decreases the supply of blood and oxygen to the heart. CAD is the leading cause of death for both men and women in the United States.3 To help to restore blood flow, a physician may use a stent (a flexible metal scaffolding) that is delivered during a minimally invasive procedure to prop open the artery. A drug-eluting stent is the most common type of stent used to treat a blockage of the heart arteries.4
"The new Onyx Frontier DES, with its enhanced deliverability, will continue to help interventional cardiologists treat complex coronary cases and larger ranges of vessel sizes more efficiently," said Azeem Latib, M.D., section head of interventional cardiology and medical director of structural heart interventions at Montefiore Medical Center in New York City. "Delivering safe and effective outcomes to our patients is our number one priority. It's important that physicians have access to tools like the Onyx Frontier DES that can allow them to efficiently achieve those outcomes."
Meaningful design changes, including increased catheter flexibility, an innovative dual-layer balloon technology and a lower crossing profile led to a 16% improvement in deliverability with Onyx Frontier vs. the previous generation Resolute Onyx DES.2 In addition to the delivery system enhancements, Onyx Frontier offers a broad size matrix to treat more patients and is the only 2.0 mm DES available in the United States (similar to Resolute Onyx). Further, Onyx Frontier continues to provide 4.50-5.00 mm sizes that can be expanded to 6.00 mm - specifically designed to support extra-large vessels. Onyx Frontier shares the same clinical indications as Resolute Onyx, including the most recent approval for patients that are at high risk of bleeding who may benefit from a dual antiplatelet therapy (DAPT) duration as short as one month.2
"The Onyx Frontier DES FDA approval is a very important milestone for Medtronic's Coronary business and demonstrates our commitment to interventional cardiologists by providing best-in-class products," said Jason Weidman, senior vice president and president of the Coronary & Renal Denervation business, which is part of the Cardiovascular Portfolio at Medtronic. "The Onyx Frontier launch also correlates directly to Medtronic's commitment to engineering. The team built upon the design and clinical successes of the Resolute Onyx DES and has continued to evolve proven DES technology to further address the needs of physicians. We look forward to continuing the pursuit of innovation each day."
The Onyx Frontier DES is now approved in the United States and is pending CE (Conformité Européene) Mark.
For more information on Medtronic (NYSE:MDT), visit www.Medtronic.com(opens new window) and follow @Medtronic(opens new window) on Twitter and LinkedIn(opens new window).
SOURCE Medtronic plc
Medtronic gets FDA approval for Onyx Frontier drug-eluting stent for coronary artery disease
May 13, 2022 8:31 AM ET
By: Ravikash, SA News Editor
- Medtronic (NYSE:MDT) said it received U.S. Food and Drug Administration (FDA) approval for its Onyx Frontier drug-eluting stent (DES).
- https://seekingalpha.com/news/3838563-medtronic-gets-fda-approval-for-onyx-frontier-drug-eluting-stent-for-coronary-artery-disease
- https://seekingalpha.com/symbol/MDT
- https://www.medtronic.com/us-en/index.html
Mounjaro™ (tirzepatide) injection
FDA approves Lilly's Mounjaro™ (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes
May 13, 2022Download PDF
Mounjaro delivered superior A1C reductions versus all comparators in phase 3 SURPASS clinical trials
While not indicated for weight loss, Mounjaro led to significantly greater weight reductions versus comparators in a key secondary endpoint
Mounjaro represents the first new class of diabetes medicines introduced in nearly a decade and is expected to be available in the U.S. in the coming weeks
INDIANAPOLIS, May 13, 2022 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) approved Mounjaro™ (tirzepatide) injection, Eli Lilly and Company's (NYSE: LLY) new once-weekly GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. Mounjaro has not been studied in patients with a history of pancreatitis and is not indicated for use in patients with type 1 diabetes mellitus.
As the first and only FDA-approved GIP and GLP-1 receptor agonist, Mounjaro is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones.1
"Mounjaro delivered superior and consistent A1C reductions against all of the comparators throughout the SURPASS program, which was designed to assess Mounjaro's efficacy and safety in a broad range of adults with type 2 diabetes who could be treated in clinical practice. The approval of Mounjaro is an exciting step forward for people living with type 2 diabetes given the results seen in these clinical trials," said Juan Pablo Frías, M.D., Medical Director, National Research Institute and Investigator in the SURPASS program.
Mounjaro will be available in six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) and will come in Lilly's well-established auto-injector pen with a pre-attached, hidden needle that patients do not need to handle or see.
The approval was based on results from the phase 3 SURPASS program, which included active comparators of injectable semaglutide 1 mg, insulin glargine and insulin degludec. Efficacy was evaluated for Mounjaro 5 mg, 10 mg and 15 mg used alone or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants in the SURPASS program achieved average A1C reductions between 1.8% and 2.1% for Mounjaro 5 mg and between 1.7% and 2.4% for both Mounjaro 10 mg and Mounjaro 15 mg. While not indicated for weight loss, mean change in body weight was a key secondary endpoint in all SURPASS studies. Participants treated with Mounjaro lost between 12 lb. (5 mg) and 25 lb. (15 mg) on average.1
Side effects reported in at least 5% of patients treated with Mounjaro include nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion (dyspepsia), and stomach (abdominal) pain. The labeling for Mounjaro contains a Boxed Warning regarding thyroid C-cell tumors. Mounjaro is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.1
"Lilly has a nearly 100-year heritage of advancing care for people living with diabetes – never settling for current outcomes. We're not satisfied knowing that half of the more than 30 million Americans living with type 2 diabetes are not reaching their target blood glucose levels," said Mike Mason, president, Lilly Diabetes. "We are thrilled to introduce Mounjaro, which represents the first new class of type 2 diabetes medication introduced in almost a decade and embodies our mission to bring innovative new therapies to the diabetes community."
Mounjaro is expected to be available in the United States in the coming weeks. Lilly is committed to helping people access the medicines they are prescribed and will work with insurers, health systems and providers to help enable patient access to Mounjaro. Lilly plans to offer a Mounjaro savings card for people who qualify. Patients or healthcare professionals with questions about Mounjaro can visit www.Mounjaro.com or call The Lilly Answers Center at 1-800-LillyRx (1-800-545-5979).
Tirzepatide is also under regulatory review for the treatment of type 2 diabetes in Europe, Japan and several additional markets. A multimedia gallery is available on Lilly.com.
About the SURPASS clinical trial program
The SURPASS phase 3 global clinical development program for tirzepatide began in late 2018 and included five global registration trials and two regional trials in Japan. These studies ranged from 40 to 52 weeks and evaluated the efficacy and safety of Mounjaro 5 mg, 10 mg and 15 mg as a monotherapy and as an add-on to various standard-of-care medications for type 2 diabetes. The active comparators in the studies were injectable semaglutide 1 mg, insulin glargine and insulin degludec. Collectively, the five global registration trials consistently demonstrated A1C reductions for participants taking Mounjaro across multiple stages of their type 2 diabetes journeys, from an average around five to 13 years of having diabetes.2-8
- SURPASS-1 (NCT03954834) was a 40-week study comparing the efficacy and safety of Mounjaro 5 mg (N=121), 10 mg (N=121) and 15 mg (N=120) as monotherapy to placebo (N=113) in adults with type 2 diabetes inadequately controlled with diet and exercise alone. From a baseline A1C of 7.9%, Mounjaro reduced participants' A1C by a mean of 1.8%* (5 mg) and 1.7%* (10 mg and 15 mg) compared to 0.1% for placebo. In a key secondary endpoint, from a baseline weight of 189 lb., Mounjaro reduced participants' weight by a mean of 14 lb.* (5 mg), 15 lb.* (10 mg) and 17 lb.* (15 mg) compared to 2 lb. for placebo.2,3
- SURPASS-2 (NCT03987919) was a 40-week study comparing the efficacy and safety of Mounjaro 5 mg (N=470), 10 mg (N=469) and 15 mg (N=469) to injectable semaglutide 1 mg (N=468) in adults with type 2 diabetes inadequately controlled with ≥1500 mg/day metformin alone. From a baseline A1C of 8.3%, Mounjaro reduced participants' A1C by a mean of 2.0%ꝉ (5 mg), 2.2%* (10 mg) and 2.3%* (15 mg) compared to 1.9% for semaglutide. In a key secondary endpoint, from a baseline weight of 207 lb., Mounjaro reduced participants' weight by a mean of 17 lb.ꝉ (5 mg), 21 lb.* (10 mg) and 25 lb.* (15 mg) compared to 13 lb. for semaglutide.4,5
- SURPASS-3 (NCT03882970) was a 52-week study comparing the efficacy of Mounjaro 5 mg (N=358), 10 mg (N=360) and 15 mg (N=358) to titrated insulin degludec (N=359) in adults with type 2 diabetes treated with metformin with or without an SGLT-2 inhibitor. From a baseline A1C of 8.2%, Mounjaro reduced participants' A1C by a mean of 1.9%* (5 mg), 2.0%* (10 mg) and 2.1%* (15 mg) compared to 1.3% for insulin degludec. From a baseline weight of 208 lb., Mounjaro reduced participants' weight by a mean of 15 lb.* (5 mg), 21 lb.* (10 mg) and 25 lb.* (15 mg) compared to an increase of 4 lb. for insulin degludec.6
- SURPASS-4 (NCT03730662) was a 104-week study comparing the efficacy and safety of Mounjaro 5 mg (N=328), 10 mg (N=326) and 15 mg (N=337) to insulin glargine (N=998) in adults with type 2 diabetes inadequately controlled with at least one and up to three oral antihyperglycemic medications (metformin, sulfonylureas or SGLT-2 inhibitors), who have increased cardiovascular (CV) risk. The primary endpoint was measured at 52 weeks. From a baseline A1C of 8.5%, Mounjaro reduced participants' A1C by a mean of 2.1%* (5 mg), 2.3%* (10 mg) and 2.4%* (15 mg) compared to 1.4% for insulin glargine. From a baseline weight of 199 lb., Mounjaro reduced weight by a mean of 14 lb.* (5 mg), 20 lb.* (10 mg) and 23 lb.* (15 mg) compared to an increase of 4 lb. for insulin glargine.7
- SURPASS-5 (NCT04039503) was a 40-week study comparing the efficacy and safety of Mounjaro 5 mg (N=116), 10 mg (N=118) and 15 mg (N=118) to placebo (N=119) in adults with inadequately controlled type 2 diabetes already being treated with insulin glargine, with or without metformin. From a baseline A1C of 8.3%, Mounjaro reduced A1C by a mean of 2.1%* (5 mg), 2.4%* (10 mg) and 2.3%* (15 mg) compared to 0.9% for placebo. From a baseline weight of 210 lb., Mounjaro reduced participants' weight by a mean of 12 lb.* (5 mg), 17 lb.* (10 mg) and 19 lb.* (15 mg) compared to an increase of 4 lb. for placebo.8
*p<0.001 for superiority vs. placebo or active comparator, adjusted for multiplicity
ꝉp<0.05 for superiority vs. semaglutide 1 mg, adjusted for multiplicity
About Mounjaro™ (tirzepatide) injection1
Mounjaro™ (tirzepatide) injection is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. As the first and only FDA-approved GIP and GLP-1 receptor agonist, Mounjaro is a single molecule that activates the body's receptors for GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1). Mounjaro will be available in six doses (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) and will come in Lilly's well-established auto-injector pen with a pre-attached, hidden needle that patients do not need to handle or see.
Learn more
For more information, call 1-800-LillyRx (1-800-545-5979) or go to www.mounjaro.com.
This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Mounjaro and how to take it. Your healthcare provider is the best person to help you decide if Mounjaro is right for you.
MounjaroTM and its delivery device base are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
Please click to access full Prescribing Information and Medication Guide.
To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY
View original content to download multimedia:https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-injection-the-first-and-only-gip-and-glp-1-receptor-agonist-for-the-treatment-of-adults-with-type-2-diabetes-301547339.html
SOURCE Eli Lilly and Company
Eli Lilly's dual-receptor diabetes drug tirzepatide granted FDA approval
May 13, 2022 3:44 PM ET
Eli Lilly and Company (LLY)NVO
By: Jonathan Block, SA News Editor2 Comments
- The U.S. FDA has approved Eli Lilly's (NYSE:LLY) Mounjaro (tirzepatide), the first-ever diabetes medication that activates glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors.
- https://seekingalpha.com/news/3838811-eli-lilly-dual-receptor-diabetes-drug-tirzepatide-mounjaro-granted-fda-approval
- https://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targeted-treatment-type-2-diabetes
- https://seekingalpha.com/symbol/LLY
- https://www.lilly.com/
Nirsevimab
PRESS RELEASESMay 11 2022
Press Release: New nirsevimab data analyses reinforce efficacy against RSV
New nirsevimab data analyses reinforce efficacy against RSV
- A prespecified pooled analysis of Phase 3 and Phase 2b data demonstrated an efficacy of 79.5% against medically attended lower respiratory tract infections (LRTI), including hospitalizations, caused by respiratory syncytial virus (RSV)1
- Nirsevimab is the first investigational immunization designed to protect all infants across the RSV season with a single dose
- Two analyses are being presented at the European Society for Paediatric Infectious Diseases meeting1,2
Paris, May 11, 2022. Results from a prespecified pooled analysis of the pivotal Phase 3 MELODY and Phase 2b nirsevimab trials demonstrated an efficacy (relative risk reduction versus placebo) of 79.5% (95% CI 65.9 to 87.7; P<0.0001) against medically attended LRTI, such as bronchiolitis or pneumonia, caused by RSV in infants born at term or preterm entering their first RSV season.1
In a separate pooled post-hoc analysis of the trials, blood samples taken from infants dosed with nirsevimab exhibited RSV neutralizing antibodies that were approximately 50-fold higher than baseline at Day 151 post-dose. RSV neutralizing antibody levels remained greater than 19-fold higher than placebo recipients with no known RSV infection through Day 361, suggesting protection may extend beyond Day 151.2
The safety profile across the nirsevimab and placebo groups, as reported in previous trials, remains similar.3-6 These findings contribute to the growing body of evidence suggesting that nirsevimab can protect all infants through their first RSV season with a single dose.1-7
Eric Simões, MD
Clinical Professor, Pediatrics-Infectious Diseases, UC Denver School of Medicine
“RSV remains the most common cause of LRTI in infants and results in seasonal epidemics globally each year. These new analyses strengthen nirsevimab’s potential to protect all infants across the RSV season with a single dose, which may lead to a paradigm shift in RSV prevention.”
Jean-François Toussaint
Global Head of Research and Development Vaccines, Sanofi
“These new analyses are very consistent with and confirm the strong results observed in all Phase 2 and Phase 3 studies that evaluated nirsevimab in diverse pediatric populations. We take pride in the progress made to develop a potential solution to address this long unmet need for all infants.”
Mene Pangalos
Executive Vice President, BioPharmaceuticals R&D, AstraZeneca
“Each year, RSV causes seasonal epidemics of LRTIs in infants. These analyses add to nirsevimab’s compelling body of evidence as the first potential single-dose preventative immunization for all infants against RSV, addressing a clear unmet need in the RSV preventative landscape.”
The data are being presented at the 40th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) from May 9-13 in Athens, Greece.
Nirsevimab is being developed by Sanofi and AstraZeneca.
About nirsevimab
Nirsevimab is an investigational long-acting antibody designed to protect all infants from birth entering their first RSV season with a single dose. Due to its extended half-life technology, nirsevimab is being developed as a single dose for protection of all infants through their first RSV season.5,6,8
Nirsevimab is an immunization designed to provide direct RSV protection to all infants via an antibody to help prevent LRTI caused by RSV. Monoclonal antibodies do not require the activation of the immune system to help offer rapid and direct protection against disease.9
In March 2017, Sanofi and AstraZeneca announced an agreement to develop and commercialize nirsevimab. Under the terms of the agreement, AstraZeneca leads all development and manufacturing activities and Sanofi will lead commercialization activities and record revenues. Under the terms of the global agreement, Sanofi made an upfront payment of €120m, has paid a development milestone of €30m and will pay up to a further €465m upon achievement of certain development and sales-related milestones. The two companies share all costs and profits. Revenue from the agreement is reported as Collaboration Revenue in the Company’s financial statements.
Nirsevimab has been granted regulatory designations to facilitate expedited development by several regulatory agencies around the world. These include Breakthrough Therapy Designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the US Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority MEdicines scheme; Promising Innovative Medicine designation by the UK Medicines and Healthcare products Regulatory Agency; and named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development (AMED). The safety and efficacy of nirsevimab is currently being evaluated under an accelerated assessment procedure by the EMA. Nirsevimab has not been approved by any regulatory authority.
About the pivotal nirsevimab clinical trials
The Phase 2b trial was a randomized, placebo-controlled trial designed to measure the efficacy of nirsevimab against medically attended LRTI through 150 days post-dose. Healthy preterm infants of 29–35 weeks’ gestation were randomized (2:1) to receive a single 50mg intramuscular injection of nirsevimab or placebo. Between November 2016 and December 2017, 1,453 infants were randomized (nirsevimab, n=969; placebo, n=484) at the RSV season start. Research was conducted in both hemispheres, at 164 sites in 23 countries.6 Data was published in the New England Journal of Medicine (NEJM) in July 2020. The dosing regimen was optimized based on further exploration of this data. The subsquent Phase 3 study MELODY applied the optimized dosing regimen.1,5
The Phase 3 MELODY trial was a randomized, placebo-controlled trial conducted across 21 countries designed to determine efficacy of nirsevimab against medically attended LRTI due to RSV confirmed by reverse transcriptase polymerase chain reaction testing through 150 days after dosing, versus placebo, in healthy late preterm and term infants (35 weeks gestational age or greater) entering their first RSV season.5 Infants were randomized (2:1) to receive a single 50mg (in infants weighing <5kg) or 100mg (in infants weighing ≥5kg) intramuscular injection of nirsevimab or placebo. Between July 2019 and March 2020, 1,490 infants were randomized to either nirsevimab or placebo at the RSV season start.3 Data was published on the primary analysis in NEJM in March 2022.
The prespecified pooled analyses of the Phase 3 and the Phase 2b trials looked at infants receiving the optimized dosing regimen (infants <5 kg at dosing and receiving the 50 mg dose from Phase 2b and the infants from Phase 3), and demonstrated an efficacy of 79.5% (95% CI 65.9 to 87.7, P<0.0001) against medically attended LRTI and 77.3% (95% CI 50.3, 89.7, P<0.001) against RSV LRTI hospitalizations. The analysis was based on 2,350 infants of which 1,564 infants were randomized to receive nirsevimab and 786 infants were randomized to receive placebo.1
The results of MELODY, Phase 2/3 MEDLEY and the Phase 2b trials demonstrate that nirsevimab provides protection against RSV in all infants entering their first RSV season with a single dose.1-5 This all-infant population includes preterm, healthy late preterm and term infants, as well as infants with specific conditions.
These trials form the basis of regulatory submissions that began in 2022.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
AstraZeneca/Sanofi's single-dose nirsevimab reduces RSV infection in infants by ~80% shows data
May 11, 2022 5:35 AM ET
By: Ravikash, SA News Editor1 Comment
AstraZeneca (NASDAQ:AZN) Sanofi's (NASDAQ:SNY) said a pooled analysis from two studies showed 79.5% efficacy of their single dose antibody nirsevimab against lower respiratory tract infections (LRTI), caused by respiratory syncytial virus (RSV), in infants.
https://seekingalpha.com/symbol/SNY
https://seekingalpha.com/symbol/AZN
lecanemab (BAN2401)
EISAI COMPLETES ROLLING SUBMISSION TO THE U.S. FDA FOR BIOLOGICS LICENSE APPLICATION OF LECANEMAB FOR EARLY ALZHEIMER’S DISEASE UNDER THE ACCELERATED APPROVAL PATHWAY
MAY 9, 2022 • INVESTOR RELATIONS
TOKYO and CAMBRIDGE, Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Michel Vounatsos, "Biogen") announced today that Eisai has completed the rolling submission to the U.S. Food and Drug Administration (FDA) of a Biologics License Application (BLA) under the accelerated approval pathway for the investigational anti-amyloid beta (Aβ) protofibril antibody lecanemab (BAN2401) for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD) with confirmed presence of amyloid pathology in the brain. As part of the completed rolling submission, Eisai has requested Priority Review. If the FDA accepts the BLA, the Prescription Drug User Fee Act (PDUFA) action date (target date for completion of examination) will be set. While Eisai is currently submitting lecanemab under the accelerated approval pathway, the lecanemab Phase 3 confirmatory Clarity AD clinical trial conducted with 1,795 patients will report out in the Fall of 2022. The FDA has agreed that the results of Clarity AD, when completed, can serve as the confirmatory study to verify the clinical benefit of lecanemab. Dependent upon the results of the Clarity AD clinical trial, Eisai may submit for full approval of lecanemab to the FDA during fiscal year 2022.
The BLA submission for lecanemab is based on clinical, biomarker and safety data from the proof-of-concept Phase 2b (Study 201 Core) in 856 people with early AD with confirmed presence of amyloid pathology, biomarker and safety data from the Study 201 OLE (open-label extension study, 180 subjects), and blinded safety data from the confirmatory Clarity AD Phase 3 study (1,795 subjects). The large number of participants across these studies provides the FDA with extensive safety data. Study 201 explored the impact of treatment with lecanemab on reducing amyloid plaque and clinical decline. At 18 months of treatment, 10 mg/kg biweekly lecanemab reduced brain amyloid by a mean of 0.306 SUVr units (from a baseline mean of 1.37), and over 80% of subjects became amyloid negative by visual read. Furthermore, the extent of reduction in amyloid was correlated with slower clinical decline on ADCOMS (Alzheimer’s Disease Composite Score), CDR-SB (Clinical Dementia Rating-Sum-of-Boxes), and ADAS-cog (Alzheimer Disease Assessment Scale-Cognitive Subscale) at the treatment group and patient level. In the Core study, the overall rate of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), an adverse event associated with anti-amyloid beta antibodies therapies was 9.9% (16/161) of patients treated with lecanemab 10 mg/kg biweekly compared with 0.8% (2/245) of placebo patients. The results from Study 201 were published in a peer-reviewed journal Alzheimer’s Research and Therapy in April 2021.
“We would like to thank the people living with early AD and the healthcare professionals who participated in the lecanemab 201 study for their cooperation allowing completion of this BLA to the U.S. FDA. Alzheimer’s disease is a progressive and devastating disease with few treatment options,” said Haruo Naito, Chief Executive Officer at Eisai Co., Ltd. “Eisai employees have spent time with people living with Alzheimer’s disease and their families to truly understand their feelings and challenges and have been working to create new treatments for many years. Our comprehensive medicine creation approach along the Alzheimer’s disease continuum reflects Eisai’s long-term commitment to providing innovative treatments to the people living with AD, their families and healthcare professionals who urgently need new treatment options.”
“With Alzheimer’s disease, patients and their loved ones don’t have the luxury of time. There is an enormous unmet need in this space, and we continue to make progress in advancing additional treatment options for people living with this devastating disease,” said Michel Vounatsos, Chief Executive Officer at Biogen. “Anti-amyloid antibodies are a new wave of important medicines, which could provide patients and their physicians more options in addressing this complex disease.”
Lecanemab was granted Breakthrough Therapy and Fast Track designations by the FDA in June and December 2021, respectively. In March 2022, Eisai initiated submission of application data to the Pharmaceuticals and Medical Devices Agency (PMDA) under the prior assessment consultation system in Japan with the aim of obtaining early approval for lecanemab, and aims to file for the manufacturing and marketing approval based on the results of Clarity AD during Eisai’s fiscal year 2022.
Eisai serves as the lead of lecanemab development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
1. About Lecanemab (BAN2401)
Lecanemab is an investigational humanized monoclonal antibody for Alzheimer’s disease (AD) that is the result of a strategic research alliance between Eisai and BioArctic. Lecanemab selectively binds to neutralize and eliminate soluble, toxic amyloid-beta (Aβ) aggregates (protofibrils) that are thought to contribute to the neurodegenerative process in AD. As such, lecanemab may have the potential to have an effect on disease pathology and to slow down the progression of the disease. Currently, lecanemab is being developed as the only anti- Aβ antibody that can be used for the treatment of early AD without the need for titration. With regard to the results from pre-specified analysis at 18 months of treatment, Study 201 demonstrated reduction of brain Aβ accumulation (P<0.0001) and slowing of disease progression measured by ADCOMS* (P<0.05) in early AD patients. The study did not achieve its primary outcome measure** at 12 months of treatment. The Study 201 open-label extension was initiated after completion of the Core period and a Gap period off treatment of 9-59 months (average of 24 months, n=180 from core study enrolled) to evaluate safety and efficacy, and is underway.
Currently, lecanemab is being studied in a confirmatory Phase 3 clinical study in symptomatic early AD (Clarity-AD), following the outcome of the Phase 2 clinical study (Study 201). Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer’s Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited Alzheimer’s disease (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing. Furthermore, Eisai has initiated a lecanemab subcutaneous dosing Phase 1 study. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement concluded with BioArctic in December 2007.
* Developed by Eisai, ADCOMS (AD Composite Score) combines items from the ADAS-Cog (Alzheimer’s Disease Assessment Scale-cognitive subscale), CDR (Clinical Dementia Rating) and the MMSE (Mini-Mental State Examination) scales to enable a sensitive detection of changes in clinical functions of early AD symptoms and changes in memory. The ADCOMS scale ranges from a score of 0.00 to 1.97, with higher score indicating greater impairment.
** An 80% or higher estimated probability of demonstrating 25% or greater slowing in clinical decline at 12 months treatment measured by ADCOMS from baseline compared to placebo.
2. About the Collaboration between Eisai and Biogen for Alzheimer’s Disease
Eisai and Biogen are collaborating on the joint development and commercialization of AD treatments. Eisai serves as the lead in the co-development of lecanemab.
3. About the Collaboration between Eisai and BioArctic for Alzheimer’s Disease
Since 2005, BioArctic has had a long-term collaboration with Eisai regarding the development and commercialization of drugs for the treatment of AD. The commercialization agreement on the lecanemab antibody was signed in December 2007, and the development and commercialization agreement on the antibody lecanemab back-up for AD, which was signed in May 2015. Eisai is responsible for the clinical development, application for market approval and commercialization of the products for AD. BioArctic has no development costs for lecanemab in AD.
4. About Eisai Co., Ltd.
Eisai Co., Ltd. is a leading global pharmaceutical company headquartered in Japan. Eisai’s corporate philosophy is based on the human health care (hhc) concept, which is to give first thought to patients and their families, and to increase the benefits that health care provides to them. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
Leveraging the experience gained from the development and marketing of a treatment for Alzheimer’s disease, Eisai aims to establish the “Eisai Dementia Platform.” Through this platform, Eisai plans to deliver novel benefits to those living with dementia and their families through constructing a “Dementia Ecosystem,” by collaborating with partners such as medical organizations, diagnostic development companies, research organizations, and bio-ventures in addition to private insurance agencies, finance industries, fitness clubs, automobile makers, retailers, and care facilities. For more information about Eisai Co., Ltd., please visit https://www.eisai.com.
5. About Biogen
As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and is providing the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing the industry’s most diversified pipeline in neuroscience that will transform the standard of care for patients in several areas of high unmet need.
In 2020, Biogen launched a bold 20-year, $250 million initiative to address the deeply interrelated issues of climate, health, and equity. Healthy Climate, Healthy Lives™ aims to eliminate fossil fuels across the company’s operations, build collaborations with renowned institutions to advance the science to improve human health outcomes, and support underserved communities.
The company routinely posts information that may be important to investors on its website at www.biogen.com. To learn more, please visit www.biogen.com and follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
Biogen, Eisai finish filing with FDA for Alzheimer’s therapy lecanemab, seek priority review
May 10, 2022 6:11 AM ET Eisai Co., Ltd. (ESALY), ESALF, BIIB
By: Ravikash, SA News Editor
Biogen (NASDAQ:BIIB) and Eisai (OTCPK:ESALY) (OTCPK:ESALF) completed a rolling submission to the U.S. Food and Drug Administration (FDA) of their medicine lecanemab to treat Alzheimer’s disease (AD).
https://seekingalpha.com/symbol/ESALY
https://seekingalpha.com/symbol/ESALF
https://seekingalpha.com/symbol/BIIB
https://www.alzforum.org/therapeutics/lecanemab
biotecMAX™ Feb/Mar/APR/May 2022 Insight
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu approved in the US for patients with HER2-positive metastatic breast cancer treated with a prior anti-HER2-based regimen
PUBLISHED5 May 2022
5 May 2022 07:10 BST
Approval broadens indication for AstraZeneca and Daiichi Sankyo’s Enhertu to earlier use in metastatic breast cancer
Based on ground-breaking DESTINY-Breast03 results showing Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1)
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The approval by the Food and Drug Administration (FDA) was based on positive results from the DESTINY-Breast03 Phase III trial that showed Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The approval was granted under the FDA’s Real-Time Oncology Review (RTOR) programme and converts the accelerated approval of Enhertu in later line HER2-positive metastatic breast cancer to standard approval, broadening Enhertu’s breast cancer indication in the US to earlier lines of use in patients with HER2-positive metastatic breast cancer.
Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program for Sarah Cannon Research Institute, Nashville, Tennessee, US, said: “Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today’s approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment.”
Catherine Ormerod, Executive Vice President, Strategy and Mission, Living Beyond Breast Cancer, said: “This is an important day for the breast cancer community. With this approval, Enhertu now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Enhertu is already established in the later-line treatment of patients with HER2-positive metastatic breast cancer, and we are thrilled that with this approval, patients in the US will now be able to access the transformative potential of Enhertu earlier in their treatment. We look forward to bringing this important, potentially paradigm-shifting medicine to even more patients across the globe in an earlier setting as quickly as possible.”
Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: “Today’s FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA’s accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer. Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to T-DM1 in an earlier setting of HER2-positive metastatic breast cancer.”
The DESTINY-Breast03 Phase III trial results were recently published online in The New England Journal of Medicine.1 In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.
Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (Enhertu) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines®) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.2
The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration and Switzerland’s Swissmedic.
This approval follows the recent Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this earlier setting.
Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.
DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate (ORR), duration of response, PFS based on investigator assessment and safety.
DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is also approved in approximately 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE:4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu wins FDA approval to treat breast cancer subtype
May 05, 2022 4:48 AM ET AstraZeneca PLC (AZN), DSNKYDSKYF
By: Ravikash, SA News Editor1 Comment
The U.S. Food and Drug Administration (FDA) approved AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat certain patients with breast cancer.
https://seekingalpha.com/symbol/DSKYF
https://seekingalpha.com/symbol/DSNKY
https://seekingalpha.com/symbol/AZN
Jakavi® (ruxolitinib) Jakafi
Novartis receives European Commission approval for Jakavi® to be the first post-steroid treatment for acute and chronic graft-versus-host disease
May 05, 2022
- Jakavi is the first JAK1/2 inhibitor available for patients in Europe who previously had no approved therapies for the treatment of steroid-refractory graft-versus-host disease (GvHD)1,2
- In clinical trials, Jakavi demonstrated superiority versus best available therapy in patients with steroid-refractory/dependent acute and chronic GvHD, with overall response rates of 62% vs. 39%, and 50% vs. 26% respectively2,3
- GvHD is a common and potentially life-threatening complication that arises in approximately half of patients following allogeneic stem cell transplants4
Basel, May 5, 2022 — Novartis today announced the European Commission (EC) has approved Jakavi (ruxolitinib) for the treatment of patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies.
“Today, 30-60% of patients with GvHD do not respond to first-line steroid treatment, underscoring the need for new approaches to ensure long-term treatment goals are met,” said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany. “The approval of Jakavi offers healthcare providers and patients with GvHD who remain dependent on or refractory to steroids a new way to manage this debilitating and life-threatening condition.”
The approval of Jakavi follows the positive opinion granted in March by the Committee for Medicinal Products for Human Use of the European Medicines Agency, based on the Phase III REACH2 and REACH3 trials in which Jakavi demonstrated superiority in overall response rate (ORR) compared to best available therapy (BAT). Results of REACH2 showed 62% ORR with Jakavi at Day 28, compared to 39% for BAT; and REACH3 demonstrated a significantly improved ORR at week 24 (50% vs. 26%) with a higher best ORR (76% vs. 60%) vs. BAT, among steroid-refractory/dependent chronic GvHD patients2,3.
“Five out of ten patients who receive allogeneic stem cell transplants experience the serious and sometimes fatal symptoms of graft-versus-host disease,” says Marie-France Tschudin, Novartis President of Innovative Medicines International and Chief Commercial Officer. “Jakavi, with this new indication in GvHD, will help to redefine treatment for patients who do not respond to first-line care.”
GvHD occurs when donor cells see the recipient's healthy cells as foreign and attack them. Symptoms of GvHD can appear in the skin, gastrointestinal tract, liver, mouth, eyes, genitals, lungs and joints. Approximately 50% of allogeneic stem cell transplant recipients will develop either acute or chronic GvHD. Both acute and chronic GvHD can be fatal and until now both have lacked an established standard of care for patients who do not adequately respond to first-line steroid treatment1,4-9. Currently, there are no other approved therapies for the treatment of GvHD after steroid failures1,2.
About Jakavi® (ruxolitinib)
Jakavi® (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease- related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF, and also for patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies. Jakavi is approved in over 100 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 85 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.
Novartis licensed ruxolitinib from Incyte for development and commercialization outside the United States. Ruxolitinib is marketed in the United States by Incyte as Jakafi® for adults with PV who have had an inadequate response to or are intolerant of hydroxyurea, for adults with intermediate or high-risk MF, for adult and pediatric patients 12 years and older with steroid-refractory acute GvHD, and adult and pediatric patients 12 years and older with chronic GvHD after failure of one or two lines of corticosteroids or other systemic therapy.
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte. The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.
Find out more at https://www.novartis.com.
https://seekingalpha.com/symbol/NVS
https://seekingalpha.com/symbol/INCY
Kymriah® (tisagenlecleucel) suspension
Novartis Kymriah® receives EC approval as first CAR-T cell therapy for adults with relapsed or refractory follicular lymphoma
May 04, 2022
- Kymriah offers patients in Europe with advanced follicular lymphoma a potentially definitive, single infusion CAR-T cell therapy with a remarkable safety profile
- Approval based on the Phase II ELARA trial showing Kymriah demonstrated high response rates in heavily pretreated patients, including an 86% overall response rate and a 69% complete response1
- Follicular lymphoma is an incurable malignancy in which patients often relapse despite treatment with several lines of therapy2,3
- Approval for relapsed or refractory follicular lymphoma is the third indication for Kymriah in the EU
Basel, May 4, 2022 — Novartis announced today that the European Commission (EC) has approved Kymriah® (tisagenlecleucel), a CAR-T cell therapy, for the treatment of adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy. The approval follows a positive opinion in March by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) and is applicable to all 27 European Union member states plus Iceland, Norway and Liechtenstein. This approval marks the third indication for Kymriah and makes it the first CAR-T cell therapy approved in the EU for these patients, which include those with r/r FL grade 1, 2 and 3A1.
“When follicular lymphoma fails to respond to treatment or comes back, it is typically more aggressive and difficult to treat; patients often end up cycling through multiple lines of therapy with decreasing benefit,” said Catherine Thieblemont, MD, PhD, Professor of Hematology in the Paris VII- University, France and Head of the Hemato-Oncology Unit of St-Louis Hospital in Paris. “The approval of Kymriah in Europe brings patients closer to a potentially definitive therapy, providing us hope for improved outcomes.”
The approval is based on the global Phase II ELARA trial showing that 86% of patients who were treated with Kymriah had a response, including 69% who had a complete response (CR)1. Prolonged durable response to treatment was demonstrated with an estimated 87% of patients who achieved a CR still in response at or more than nine months after initial response1. In the trial, 94 infused patients were evaluated for efficacy with a median follow-up of approximately 21 months1.
Among 97 patients evaluable for safety, the safety profile of Kymriah was remarkable1. Cytokine release syndrome (CRS) was reported in 50% of patients after Kymriah infusion, and no Grade 3 or 4 events were reported, as defined by the Lee scale1. Neurological adverse reactions occurred in 9% of patients (1% were Grade 3 or 4) within eight weeks after Kymriah infusion1. Severe infections (Grade 3 or 4) occurred in 16% of patients1.
“With this approval, we are pleased to be able to offer this transformative therapy to more people across the globe living with this advanced blood cancer,” said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. “With long-lasting responses and a safety profile that allows for flexible administration, we are striving to rewrite cancer survival and alleviate the burden of this disease for patients and the healthcare system.”
In addition to r/r FL, Kymriah is approved for the treatment of pediatric and young adult patients up to and including 25 years of age with B cell acute lymphoblastic leukemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse, and adult patients with r/r diffuse large B cell lymphoma (DLBCL) after two or more lines of systemic therapy1.
About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.
Novartis is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
Novartis CAR-T cell therapy Kymriah gets approval in EU for blood cancer subtype
May 05, 2022 5:54 AM ET Novartis AG (NVS)
By: Ravikash, SA News Editor
- The European Commission (EC) approved Novartis' (NYSE:NVS) CAR-T cell therapy Kymriah to treat adult patients with relapsed or refractory (r/r) follicular lymphoma (FL) after two or more lines of systemic therapy.
- https://seekingalpha.com/news/3833059-novartis-car-t-cell-therapy-kymriah-gets-approval-in-eu-for-blood-cancer-subtype
- https://seekingalpha.com/symbol/NVS
- https://www.us.kymriah.com/
- https://www.novartis.us/sites/www.novartis.us/files/kymriah.pdf
Farxiga (dapagliflozin)
Farxiga met primary endpoint in DELIVER Phase III trial, reducing risk of cardiovascular death or worsening heart failure in patients with preserved ejection fraction
PUBLISHED5 May 2022
5 May 2022 07:05 BST
Results from the DELIVER and DAPA-HF Phase III trials demonstrate Farxiga’s efficacy in heart failure regardless of ejection fraction
High-level results from the DELIVER Phase III trial showed AstraZeneca’s Farxiga (dapagliflozin) reached a statistically significant and clinically meaningful reduction in the primary composite endpoint of cardiovascular (CV) death or worsening heart failure (HF). The trial was conducted in patients with HF with mildly reduced or preserved ejection fraction (defined as left ventricular ejection fraction [LVEF] greater than 40%).
HF is a chronic, long-term condition that worsens over time1. It affects nearly 64 million people globally2 and is associated with substantial morbidity and mortality3. There are several main categories of HF related to ejection fraction (EF), a measurement of the percentage of blood leaving the heart each time it contracts including: HF with reduced EF (HFrEF) (LVEF less than or equal to 40%), HF with mildly reduced EF (HFmrEF) (LVEF 41-49%) and preserved EF (HFpEF) (LVEF greater than or equal to 50%)4. Approximately half of all HF patients have mildly reduced or preserved EF with few therapeutic options available4,5. Farxiga already has approved indications relating to the treatment of type-2 diabetes (T2D), HFrEF and chronic kidney disease (CKD).
Dr. Scott Solomon, Professor of Medicine at Harvard Medical School and Brigham and Women’s Hospital and Principal Investigator of the DELIVER Phase III trial, said: “We are delighted to have met the primary endpoint in this patient population which has few treatment options. DELIVER is the largest and broadest trial to date in heart failure with mildly reduced or preserved ejection fraction. The results of DELIVER extend the benefit of dapagliflozin to the full spectrum of patients with heart failure.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "Today’s groundbreaking results coupled with those from the DAPA-HF trial show that Farxiga is effective in treating heart failure regardless of ejection fraction. These data build upon our previous studies demonstrating cardiorenal protection across patients with either diabetes, chronic kidney disease or heart failure.”
The safety and tolerability profile of Farxiga in the DELIVER Phase III trial were consistent with the well-established safety profile of the medicine.
The full DELIVER Phase III trial results will be submitted for presentation at a forthcoming medical meeting and regulatory submissions will be made in the coming months.
DELIVER
DELIVER was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of Farxiga, compared with placebo, in the treatment of HF patients with LVEF greater than 40% with or without T2D. Farxiga was given once daily in addition to background therapy (regional standard of care for all comorbidities, including diabetes and hypertension, with the exception of concomitant use of a sodium-glucose cotransporter 2 [SGLT2] inhibitor)13. DELIVER is the largest clinical trial to date in HF patients with EF above 40%, with 6,263 randomised patients13,14.
The primary endpoint was the time to first occurrence of CV death, hospitalisation for HF (hHF) or an urgent HF visit. The secondary endpoint includes the total number of HF events (hHF or urgent HF visit) and CV death, change from baseline in the total symptom score of the Kansas City Cardiomyopathy Questionnaire at eight months, time to the occurrence of CV death and time to the occurrence of death from any cause13.
Farxiga
Farxiga (dapagliflozin) is a first-in-class, oral, once-daily SGLT2 inhibitor. Research has shown Farxiga’s efficacy in preventing and delaying cardiorenal disease, while also protecting the organs – important findings given the underlying links between the heart, kidneys and pancreas15-17. Damage to one of these organs can cause the other organs to fail, contributing to leading causes of death worldwide, including T2D, HF and CKD2,18-20.
In the US, Farxiga is approved as an adjunct to diet and exercise to improve glycaemic control in adults with T2D and in T2D to reduce the risk of hHF or CV death when added to standard of care based on the findings of the DECLARE-TIMI 58 Phase III CV outcomes trial17. Farxiga is also approved for the treatment of HFrEF and the treatment of CKD based on the findings of the DAPA-HF and DAPA-CKD Phase III trials. In the European Union, Forxiga is indicated as both monotherapy (when metformin is appropriate) and as part of combination therapy for the treatment of insufficiently controlled T2D, with the additional benefits of weight loss and blood-pressure reduction, as an adjunct to diet and exercise in adults with T2D. Forxiga is also approved for the treatment of symptomatic chronic HFrEF in adults with and without T2D and for the treatment of CKD in adults with and without T2D.
DapaCare is a robust programme of clinical trials to evaluate the potential CV, renal and organ protection benefits of Farxiga. It includes more than 35 completed and ongoing Phase IIb/III trials in more than 35,000 patients, as well as more than 2.5 million patient-years’ experience. Farxiga is currently being tested in the DAPA-MI Phase III trial - a first of its kind, indication-seeking registry-based randomised controlled trial in patients without T2D following an acute myocardial infarction (MI) or heart attack21.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca Farxiga cuts risk of death/heart failure in certain patients in late-stage study
May 05, 2022 7:57 AM ET
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) said data from a late-stage study showed that its drug Farxiga helped reduce the risk of death or heart failure (HF) in certain patients.
https://seekingalpha.com/symbol/AZN
RINVOQ® (upadacitinib)
April 29, 2022
RINVOQ® (upadacitinib) Approved by U.S. FDA as an Oral Treatment for Adults with Active Ankylosing Spondylitis
- Across the two pivotal trials, RINVOQ delivered rapid and meaningful disease control with nearly half of ankylosing spondylitis (AS) patients achieving ASAS40 (51% and 44.5% with RINVOQ versus 26% and 18.2% with placebo) at week 14 compared to placebo1
- RINVOQ demonstrated significant improvement in signs and symptoms of AS at week 141-4
- FDA approval in AS marks the fifth indication for RINVOQ in chronic immune-mediated diseases1
NORTH CHICAGO, Ill., April 29, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the U.S. Food and Drug Administration (FDA) has approved RINVOQ® (upadacitinib; 15 mg, once daily) for the treatment of adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.1
"Ankylosing spondylitis is a debilitating disease that often affects younger adults and, over time, can result in lasting structural damage that can take an emotional toll on a patient's life," said Thomas Hudson, M.D., senior vice president, research and development, chief scientific officer, AbbVie. "This latest approval demonstrates another important step forward in our mission to advance the standards of care in rheumatic diseases."
The FDA approval in AS is supported by efficacy and safety data from the Phase 3 SELECT-AXIS 2 clinical trial (Study 1) evaluating RINVOQ in patients who had an inadequate response or intolerance to one or two biologic disease-modifying anti-rheumatic drugs (bDMARDs) and the Phase 2/3 SELECT-AXIS 1 clinical trial evaluating RINVOQ in patients who were naïve to bDMARDs and had an inadequate response or intolerance to at least two nonsteroidal anti-inflammatory drugs (NSAIDs).1-3
"Many patients with ankylosing spondylitis do not achieve disease control with current biologic therapies and additional treatments are needed to help relieve the signs and symptoms of this disease," said Atul Deodhar, M.D., professor of medicine and medical director of the Rheumatology Clinics for the Division of Arthritis and Rheumatic Diseases at Oregon Health & Science University, and investigator of the SELECT-AXIS 1 trial. "With today's FDA approval, patients who do not respond to a TNF inhibitor have an additional oral treatment option, in partnership with their rheumatologist, to help take control of this disease."
In both SELECT-AXIS 1 and SELECT-AXIS 2 clinical trials, a significantly greater proportion of patients receiving RINVOQ 15 mg achieved an ASAS40* response, the primary endpoint, (51% and 44.5%, respectively) compared to those receiving placebo (26% and 18.2%, respectively) at week 14. Clinical responses were observed as early as week four in SELECT-AXIS 2 for ASAS40.1,3
"Currently, there are limited treatment options for people living with ankylosing spondylitis, particularly when painful symptoms persist despite being on a TNF blocker treatment," said Cassie Shafer, chief executive officer, Spondylitis Association of America (SAA). "The approval of a new medicine is welcome news to our community of patients, offering the potential to help more people find meaningful relief from the symptoms of AS and to help reach their treatment goals."
AS is a chronic inflammatory musculoskeletal disease primarily affecting the spine and characterized by debilitating symptoms of inflammatory back pain, stiffness and restricted mobility. An estimated one out of every 200 adults in the U.S., or approximately 1.1 million people, is affected by AS.5
Additional study results include the following:
Improvement in AS Signs & Symptoms at Week 141-3
Treatment with RINVOQ 15 mg resulted in improvements in the signs and symptoms of AS, including total back pain, as well as improvements in physical function (Bath Ankylosing Spondylitis Functional Index (BASFI)) and disease activity (Patient Global Assessment of Disease Activity) versus placebo at week 14.
In SELECT-AXIS 2, patients receiving RINVOQ 15 mg at week 14 experienced:
- A significantly greater mean decrease from baseline in Total Back Pain (-3.1 change from baseline) compared to those receiving placebo (-1.5).6
- A significantly greater improvement in physical function (-2.3 change from baseline) as assessed by mean change from baseline in BASFI compared to patients on placebo (-1.09).6
*ASAS40 is a composite index that measures disease activity.2 To achieve an ASAS40 response, a patient's disease activity must have improved by at least 40%, as well as improved by two units in at least three of four disease areas assessed, and the remaining area must not have gotten worse, including back pain, patient global assessment of disease activity, physical functional and morning stiffness.2
About SELECT-AXIS 1 and SELECT-AXIS 2 trial programs2,3
SELECT-AXIS 1 is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the safety and efficacy of RINVOQ in adult patients with active ankylosing spondylitis (AS) who are bDMARD-naïve and had inadequate response to at least two NSAIDs or intolerance to/contraindication for NSAIDs. Period 2 is an open-label extension period to evaluate the long-term safety, tolerability and efficacy of RINVOQ in subjects who completed Period 1. More information on this trial can be found at www.clinicaltrials.gov (NCT03178487).
SELECT-AXIS 2 was conducted as a master study protocol that contains two standalone studies with randomization, data collection, analysis and reporting conducted independently. The Phase 3, randomized, placebo-controlled, double-blind studies are evaluating the efficacy and safety of RINVOQ compared with placebo on reduction of signs and symptoms in adult participants with active axial spondyloarthritis (axSpA), including bDMARD-IR AS (Study 1) and non-radiographic axial spondyloarthritis (nr-axSpA) (Study 2). More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT04169373).
In both clinical trials, the primary endpoint was the percentage of subjects achieving an ASAS40 response after 14 weeks of treatment with RINVOQ versus placebo.
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.1 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.
In the U.S., RINVOQ 15 mg is approved for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers; adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers; and adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.1 RINVOQ 45 mg is approved for use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers as an induction therapy once daily for 8 weeks. The recommended dose of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dosage needed to maintain response. RINVOQ 15 mg once daily can also be initiated in adults and children 12 years of age and older weighing at least 40 kg with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other system drug products, including biologics or when use of those therapies is inadvisable. In these children and adults less than 65 years of age who do not achieve an adequate response, the dose may be increased to 30 mg once daily.
Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.7-13
RINVOQ® (upadacitinib) U.S. Use and Important Safety Information1
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with active psoriatic arthritis when 1 or more tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
- Adults with active ankylosing spondylitis when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, or ankylosing spondylitis.
- Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis) that did not respond to previous treatment and whose eczema is not well controlled with other pills or injections, including biologic medicines, or when the use of other pills or injections is not recommended.
RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.
It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.
For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
SOURCE AbbVie
AbbVie announces FDA approval of Rinvoq for new arthritic indication
Apr. 29, 2022 3:09 PM ET
By: Dulan Lokuwithana, SA News Editor3 Comments
- AbbVie (NYSE:ABBV) announced on Friday that the U.S. Food and Drug Administration (FDA) approved its JAK inhibitor Rinvoq (upadacitinib) for the treatment of adults with active ankylosing spondylitis (AS), a rare form of arthritis that leads to pain and stiffness in the spine.
- https://seekingalpha.com/news/3829620-abbv-stock-slips-despite-fda-approval-of-rinvoq-for-new-arthritic-indication
- https://seekingalpha.com/symbol/ABBV
- https://www.abbvie.com/
- https://www.rinvoq.com/
BLINCYTO® (Blinatumomab)
BeiGene Announces the Approval in China of BLINCYTO® (Blinatumomab) for Injection for Pediatric Patients with Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (ALL)
May 04, 2022 5:53 AM
CAMBRIDGE, Mass. & BASEL, Switzerland & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, today announced that the China National Medical Products Administration (NMPA) has granted conditional approval of BLINCYTO® (blinatumomab) for injection for the treatment of pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL). The NMPA granted conditional approval for adult patients in this indication in December 2020.
Developed by Amgen and licensed to BeiGene in China under a strategic collaboration commenced in 2020, this is the second approval for BLINCYTO in China. The pediatric Supplemental Biologic License Application (sBLA) was submitted by BeiGene.
“This approval of BLINCYTO provides us with an opportunity to offer pediatric patients in China with relapsed or refractory B-cell precursor ALL the first approved biospecific immunotherapy treatment option for their disease,” commented Xiaobin Wu, Ph.D., President, Chief Operating Officer, and General Manager of China, at BeiGene. “We are proud to be able to offer BLINCYTO to help these young patients as they fight this disease. Our commercial organization of more than 3,100 people in China is excited to add this BLINCYTO indication to our portfolio, which includes 16 approved cancer treatments.”
BLINCYTO for injection for the treatment of adult patients with R/R CD19-positive B-cell precursor ALL was approved conditionally based on ex-China data and interim analysis results of the Phase 3 clinical trial of adult patients in China (NCT03476239). This conditional approval in pediatric patients with the above indication was granted based on ex-China research data and Chinese adult data. The full approval in this indication will depend on the results of a post-marketing study in China.
About BLINCYTO® (blinatumomab)
BLINCYTO is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.
BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:
- relapsed or refractory CD-19 positive B-cell precursor ALL in adults and children.
- CD-19 positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and children. This indication is approved under accelerated approval based on MRD response rate and hematological relapse-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:
- adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
- adults with Philadelphia chromosome negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
- pediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation
- pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome negative CD19 positive B-precursor ALL as part of the consolidation therapy.
In China, BLINCYTO is indicated for the treatment of adult patients with relapsed or refractory B-cell precursor ALL.
To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.
BLINCYTO® and BiTE® are registered trademarks of Amgen Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220504005602/en/
Source: BeiGene
Amgen, BeiGene's Blincyto gets conditional approval in China to treat blood cancer subtype in children
May 04, 2022 6:30 AM ET
By: Ravikash, SA News Editor
- China's National Medical Products Administration (NMPA) granted conditional approval to BeiGene (NASDAQ:BGNE) and Amgen's (NASDAQ:AMGN) Blincyto injection to treat children with relapsed or refractory (R/R) CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL).
- https://seekingalpha.com/news/3831802-amgen-beigenes-blincyto-gets-conditional-approval-in-china-to-treat-blood-cancer-subtype-in-children
- https://seekingalpha.com/symbol/BGNE
- https://seekingalpha.com/symbol/AMGN
- https://www.beigene.com/
- https://www.amgen.com/
- https://www.blincyto.com/
Imfinzi (durvalumab) plus chemotherapy
Imfinzi plus chemotherapy granted Priority Review in the US for patients with locally advanced or metastatic biliary tract cancer based on TOPAZ-1 Phase III trial
PUBLISHED4 May 2022
4 May 2022 07:00 BST
First Phase III trial in this setting to show improved overall survival with an immunotherapy added to chemotherapy over standard-of-care chemotherapy alone
AstraZeneca’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab), in combination with standard-of-care chemotherapy, has been accepted and granted Priority Review in the US for patients with locally advanced or metastatic biliary tract cancer (BTC).
The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the third quarter of 2022.
BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder. 2,3 Approximately 23,000 people in the US are diagnosed with BTC each year.2 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.4
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting. We are working closely with the FDA to bring the first immunotherapy-based option to patients with this devastating cancer and potentially set a new standard of care with Imfinzi plus chemotherapy.”
The sBLA was based on results from an interim analysis of the TOPAZ-1 Phase III trial presented during the 2022 American Society of Clinical Oncology Gastrointestinal Cancers (ASCO GI) Symposium. The data showed Imfinzi plus chemotherapy (gemcitabine plus cisplatin) reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI], 0.66-0.97; 2-sided p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were alive at two years compared to one in 10 (10%) treated with chemotherapy alone.
Results also showed a statistically significant 25% reduction in the risk of disease progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI, 0.64-0.89; 2-sided p=0.001). The Imfinzi combination was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.
In December 2020, Imfinzi was granted Orphan Drug Designation in the US for the treatment of BTC.
TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.
The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.
Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.
Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with small cell lung cancer (SCLC), NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.
In the past year, Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca's Imfinzi gets FDA priority review for biliary tract cancer
May 05, 2022 6:08 AM ET AstraZeneca PLC (AZN) By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration granted priority review to AstraZeneca's (NASDAQ:AZN) Imfinzi, in combination with standard-of-care chemotherapy, to treat patients with locally advanced or metastatic biliary tract cancer (BCT).
- https://seekingalpha.com/news/3833069-astrazenecas-imfinzi-gets-fda-priority-review-for-biliary-tract-cancer
- https://seekingalpha.com/symbol/AZN
- https://www.astrazeneca.com
- https://www.imfinzi.com/
Zuranolone (SAGE-217/BIIB125)
May 2, 2022
Sage Therapeutics and Biogen Initiate Rolling Submission of New Drug Application (NDA) to U.S. Food and Drug Administration for Zuranolone for the Potential Treatment of Major Depressive Disorder (MDD)
The companies expect to complete submission of the NDA for treatment of MDD in the second half of 2022; associated filing for postpartum depression anticipated in the first half of 2023
CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 2, 2022-- Sage Therapeutics, Inc. (Nasdaq: SAGE) and Biogen Inc. (Nasdaq: BIIB) initiated a rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for zuranolone in the treatment of major depressive disorder (MDD). Zuranolone is an investigational two-week, once-daily oral drug being developed for MDD and postpartum depression (PPD). The companies have submitted the nonclinical module of the NDA to the FDA and plan to submit the remaining components for the MDD filing in the second half of 2022.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220429005707/en/
Data from the completed studies of zuranolone in the LANDSCAPE and NEST clinical development programs, including data from the ongoing open-label SHORELINE Study in MDD, as well as data from the completed clinical pharmacology studies, will comprise the full submission package. The rolling submission process allows completed sections of an NDA to be submitted to the FDA for review on an ongoing basis.
“There are millions of people living with depression and the initiation of the rolling NDA submission brings us one step closer to our goal of offering zuranolone as a potential new treatment option,” said Barry Greene, Chief Executive Officer at Sage. “We believe the results from the LANDSCAPE and NEST programs, in which zuranolone demonstrated rapid and sustained effects and a well-tolerated safety profile in clinical trials, support zuranolone as a potential novel treatment option for MDD, if approved. We look forward to providing an update when the rolling submission for zuranolone in MDD is complete, which we expect to occur in the second half of this year.”
“Zuranolone has the potential to help address a significant unmet medical need in depression as an innovative option in a therapeutic area where little has changed in the past 30 years,” said Priya Singhal, M.D., M.P.H., Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “We are committed to advancing the science and developing new approaches to treating mental health, a major public health challenge that was exacerbated by the COVID-19 pandemic.”
Zuranolone was granted Fast Track Designation by the FDA in 2017 in MDD and Breakthrough Therapy Designation in 2018. Sage and Biogen plan to submit an associated NDA filing for PPD in the first half of 2023.
About Zuranolone
Zuranolone (SAGE-217/BIIB125) is a once-daily, two-week, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an investigational oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. Zuranolone has been granted Fast Track and Breakthrough Therapy Designation for MDD and Fast Track Designation for PPD by the U.S. Food & Drug Administration.
Zuranolone is being evaluated in the LANDSCAPE and NEST clinical development programs. The two development programs include multiple studies examining use of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. The LANDSCAPE program includes five studies of zuranolone in people with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two placebo-controlled studies of zuranolone in people with PPD (ROBIN and SKYLARK Studies). Additionally, Shionogi completed a Phase 2 study of zuranolone in Japan in people with MDD.
For more information, please visit www.sagerx.com.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Twitter, LinkedIn, Facebook, YouTube.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220429005707/en/
Source: Sage Therapeutics, Inc.
Sage, Biogen begin rolling submission with FDA for zuranolone to treat depression
May 02, 2022 7:18 AM ET
Sage Therapeutics, Inc. (SAGE), BIIB
By: Ravikash, SA News Editor
- Sage Therapeutics (NASDAQ:SAGE) and Biogen (NASDAQ:BIIB) began a rolling submission of a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) for approval of zuranolone to treat major depressive disorder (MDD).
- https://seekingalpha.com/news/3829885-sage-biogen-begin-rolling-submission-with-fda-for-zuranolone-to-treat-depression
- https://seekingalpha.com/symbol/SAGE
- https://seekingalpha.com/symbol/BIIB
- https://www.sagerx.com/
- https://www.sagerx.com/programs-research/pipeline/
VBI Vaccines Announces European Commission Marketing Authorisation for PreHevbri™, a 3-Antigen Adult Hepatitis B Vaccine
May 2, 2022 | Hepatitis B, Press Releases
- PreHevbri™ is the only approved 3-antigen hepatitis B vaccine for adults in the EU and EEA
- Approval follows the positive opinion granted by European Committee for Medicinal Products for Human Use (CHMP) in February 2022
- Regulatory review in the United Kingdom is ongoing as part of the European Commission Decision Reliance Procedure
VBI Vaccines Inc. (Nasdaq: VBIV) (VBI), a biopharmaceutical company driven by immunology in the pursuit of powerful prevention and treatment of disease, today announced that the European Commission (EC) has granted Marketing Authorisation for PreHevbri™ [Hepatitis B vaccine (recombinant, adsorbed)] for active immunisation against infection caused by all known subtypes of the hepatitis B virus (HBV) in adults. It can also be expected that hepatitis D will be prevented by immunisation with PreHevbri as hepatitis D (caused by the delta agent) does not occur in the absence of hepatitis B infection. The use of PreHevbri should be in accordance with official recommendations. PreHevbri contains the full antigenic composition of the hepatitis B virus surface antigen, including the S, pre-S2, and pre-S1 HBV surface antigens, and is the only approved 3-antigen HBV vaccine for adults in the European Union (EU) and in the European Economic Area (EEA) countries – Iceland, Liechtenstein, and Norway.
“We are excited to be able to announce the approval of PreHevbri in Europe, marking our second major approval for this differentiated HBV vaccine in five months, following the U.S. FDA approval at the end of November last year,” said Jeff Baxter, VBI’s President and CEO. “Hepatitis B is a highly infectious, under-reported, persistent public health problem in Europe and we believe PreHevbri has the potential to be a meaningful new tool for healthcare providers as they endeavor to fight it. We are committed to being part of this fight and are working hard to make PreHevbri available in different European countries as quickly as possible.”
The European Commission’s centralized marketing authorisation is valid in all EU Member States as well as in the European Economic Area (EEA) countries (Iceland, Liechtenstein, and Norway). VBI expects to make PreHevbri available in certain European countries beginning at the end of 2022.
The approval follows a positive opinion granted in February 2022 by the EMA’s Committee for Medicinal Products for Human Use (CHMP), which was based on the positive results from two pivotal, randomized, double-blind, controlled Phase 3 clinical studies, PROTECT and CONSTANT. Data from these studies were published, respectively, in The Lancet Infectious Diseases in May 2021 and The Journal of the American Medical Association Network Open in October 2021. Both studies compared PreHevbri to Engerix-B, a single-antigen HBV vaccine. Results from the PROTECT study showed that PreHevbri elicited higher rates of seroprotection in all subjects age 18+ (91.4% vs. 76.5%), including in adults age 45+ (89.4% vs. 73.1%). The integrated safety analysis of both studies demonstrated good tolerability with no unexpected reactogenicity. The most common adverse events in all age groups were injection site pain and tenderness, myalgia, and fatigue, all which generally resolved without intervention in 1-2 days.
VBI continues to support the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) review as part of the EC Decision Reliance Procedure (ECDRP), which was initiated upon receipt of the positive CHMP opinion in February.
About Hepatitis B
Hepatitis B is one of the world’s most significant infectious disease threats with more than 290 million people infected globally. HBV infection is the leading cause of liver disease and, with current treatments, it is very difficult to cure, with many patients going on to develop liver cancers. An estimated 900,000 people die each year from complications of chronic HBV such as liver decompensation, cirrhosis, and hepatocellular carcinoma.
About PreHevbri™
VBI’s hepatitis B vaccine is the only 3-antigen hepatitis B vaccine, comprised of the three hepatitis B surface antigens of the hepatitis B virus – S, pre-S1, and pre-S2. It is approved for use in the European Union/European Economic Area, the United States, and Israel. The brand names for this vaccine are : PreHevbri™ (EU/EEA), PreHevbrio™ (US), and Sci-B-Vac® (Israel).
Full European Summary of Product Characteristics for PreHevbri are available from the EMA website at www.ema.europa.eu.
Please visit www.PreHevbrio.com for U.S. Important Safety Information for PreHevbrio™ [Hepatitis B Vaccine (Recombinant)], or please see U.S. Full Prescribing Information.
VBI is headquartered in Cambridge, Massachusetts, with research operations in Ottawa, Canada, and a research and manufacturing site in Rehovot, Israel. For more information, visit www.vbivaccines.com.
VBI Vaccines stock rises as hepatitis B shot PreHevbri gets approval in EU
May 02, 2022 8:58 AM ET
By: Ravikash, SA News Editor
- VBI Vaccines (NASDAQ:VBIV) said the European Commission (EC) granted marketing authorization to its vaccine PreHevbri for active immunization against infection caused by all known subtypes of the hepatitis B virus (HBV) in adults.
- https://seekingalpha.com/news/3829970-vbi-vaccines-stock-rises-as-hepatitis-b-shot-prehevbri-gets-approval-in-eu
- https://seekingalpha.com/symbol/VBIV
- https://www.prehevbrio.com/
- https://www.vbivaccines.com/
KEYTRUDA® (pembrolizumab)
European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) for Patients With Microsatellite Instability-High (MSI-H) or Deficient Mismatch Repair (dMMR) Tumors in Five Different Types of Cancer
April 29, 2022 6:45 am ET
KEYTRUDA is the First Immunotherapy to be Approved for Patients with MSI-H/dMMR Biomarkers in Five Different Types of Cancer in Europe
KENILWORTH, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy. This is the second approval for KEYTRUDA in Europe based on the MSI-H/dMMR biomarker. KEYTRUDA is also approved for the first-line treatment of metastatic MSI-H or dMMR colorectal cancer in adults.
“Our company has a strong track record of applying precision medicine, through biomarkers like MSI-H and dMMR, to help identify patients most likely to respond to KEYTRUDA based on the genetic makeup of their individual cancer,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “For patients with MSI-H/dMMR colorectal cancer, KEYTRUDA monotherapy was approved in Europe as a first-line option in January 2021. Building on that approval, we are pleased that KEYTRUDA is now approved for the treatment of additional MSI-H/dMMR tumors, in certain second- or later-line patients with colorectal, endometrial, gastric, small intestine or biliary cancer.”
“In the two studies supporting this approval, KEYTRUDA monotherapy showed strong objective response rates and durability of response in patients with five different types of MSI-H/dMMR cancers,” said Dr. Aurélien Marabelle, Immuno-Oncologist at Gustave Roussy Cancer Center and Professor of Clinical Immunology at the University of Paris Saclay. “The EU approval of KEYTRUDA is an important milestone for patients living with these MSI-H/dMMR cancers who have had few treatment options and face worse outcomes when diagnosed at an advanced stage.”
This approval allows marketing of KEYTRUDA monotherapy in all 27 European Union (EU) member states plus Iceland, Lichtenstein, Norway and Northern Ireland.
Data Supporting the European Approval
The approval was based on data from KEYNOTE-164 (NCT02460198) and KEYNOTE-158 (NCT02628067), multicenter, non-randomized, open-label Phase 2 trials evaluating KEYTRUDA in patients with advanced MSI-H or dMMR solid tumors. The KEYNOTE-164 trial enrolled 124 patients with unresectable or metastatic MSI-H or dMMR colorectal cancer that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. The KEYNOTE-158 trial enrolled 355 patients with unresectable or metastatic MSI-H or dMMR solid tumors, including endometrial, gastric, small intestine or biliary cancer. Microsatellite instability or MMR tumor status was determined by prospectively using polymerase chain reaction or immunohistochemistry, respectively. Patients received KEYTRUDA 200 mg administered intravenously every three weeks until unacceptable toxicity or disease progression. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Patients without disease progression were treated for up to 24 months (up to 35 cycles). The primary efficacy outcome measure for the trials was objective response rate (ORR) as assessed by blinded independent central review using RECIST v1.1. The secondary efficacy outcome measures for the trials included duration of response (DOR), progression-free survival and overall survival.
Efficacy results from the KEYNOTE-164 and KEYNOTE-158 trials are summarized below. For patients with:
- Colorectal cancer (n=124), the ORR was 34% (95% CI, 25.6-42.9), including a complete response (CR) rate of 10% and a partial response (PR) rate of 24%, at a median follow-up time of 37.3 months (range, 0.1 to 65.2). Median DOR was not reached (range, 4.4 to 58.5+ months), and of responding patients, 92% had responses lasting at least three years.
- Endometrial cancer (n=83), the ORR was 51% (95% CI, 39.4-61.8), including a CR rate of 16% and a PR rate of 35%, at a median follow-up time of 21.9 months (range, 1.5 to 64.0). Median DOR was not reached (range, 2.9 to 60.4+ months), and of responding patients, 85% had responses lasting at least one year, and 60% had responses lasting at least three years.
- Gastric cancer (n=51), the ORR was 37% (95% CI, 24.1-51.9), including a CR rate of 14% and a PR rate of 24%, at a median follow-up time of 13.9 months (range, 1.1 to 66.9). Median DOR was not reached (range, 6.2 to 63.0+ months), and of responding patients, 90% had responses lasting at least one year, and 81% had responses lasting at least three years.
- Small intestine cancer (n=27), the ORR was 56% (95% CI, 35.3-74.5), including a CR rate of 15% and a PR rate of 41%, at a median follow-up time of 29.1 months (range, 4.2 to 67.7). Median DOR was not reached (range, 3.7+ to 57.3+ months), and of responding patients, 93% had responses lasting at least one year, and 73% had responses lasting at least three years.
- Biliary cancer (n=22), the ORR was 41% (95% CI, 20.7-63.6), including a CR rate of 14% and a PR rate of 27%, at a median follow-up time of 19.4 months (range, 1.1 to 60.8). Median DOR was 30.6 months (range, 6.2 to 46.0+), and of responding patients, 89% had responses lasting at least one year, and 42% had responses lasting at least three years.
The safety of KEYTRUDA as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of renal cell carcinoma across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks or 10 mg/kg bw every two or three weeks) in clinical studies. In this patient population, the most frequent adverse reactions with KEYTRUDA were fatigue (31%), diarrhea (22%) and nausea (21%). The majority of adverse reactions reported for KEYTRUDA monotherapy were of Grades 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions. The incidences of immune-related adverse reactions were 36.1% for all Grades and 8.9% for Grades 3-5 for KEYTRUDA monotherapy in the adjuvant setting (n=1,480) and 24.2% for all Grades and 6.4% for Grades 3-5 for KEYTRUDA monotherapy in the metastatic setting (n=5,375). No new immune-related adverse reactions were identified in the adjuvant setting.
About Microsatellite Instability-High (MSI-H) and Deficient Mismatch Repair (dMMR)
Microsatellite instability (MSI) and deficient mismatch repair (dMMR) are biomarkers that have been identified in many different types of cancer and that can be hereditary or random. MSI is a change that occurs in the DNA of certain cells, such as cancer cells, in which the number of repeated DNA bases in a microsatellite (which is a short, repeated sequence of DNA) is different from what it was when the microsatellite was inherited. dMMR describes cells that have mutations in certain genes involved in correcting mistakes made when DNA is copied into a cell when dividing. High levels of MSI (MSI-H) and dMMR can occur when a cell is unable to repair mistakes during that division process.
About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
Merck wins European approval to market Keytruda for more cancer indications
Apr. 29, 2022 7:09 AM ET
By: Dulan Lokuwithana, SA News Editor
- Merck (NYSE:MRK) announced on Friday that the European Commission approved its anti-PD-1 therapy, Keytruda for a few more indications in cancer.
- https://seekingalpha.com/news/3829276-merck-wins-european-approval-to-market-keytruda-for-more-cancer-indications
- https://seekingalpha.com/symbol/MRK
- https://www.keytruda.com/
- https://www.merck.com/
Evrysdi® (risdiplam)
Thursday, Apr 28, 2022
New Three-Year Data for Genentech’s Evrysdi (risdiplam) Show Long-Term Improvements in Survival and Motor Milestones in Babies With Type 1 Spinal Muscular Atrophy (SMA)
91% of infants treated with Evrysdi in the FIREFISH study were still alive at three years
Infants treated with Evrysdi maintained or continued to improve in measures of motor function, including their ability to sit without support for 5 and 30 seconds
Evrysdi has proven efficacy in infants and adults, with more than 5,000 patients treated to date
South San Francisco, CA -- April 28, 2022 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new three-year data from the FIREFISH study, including one-year data from the open label extension, reinforcing the long-term efficacy and safety of Evrysdi® (risdiplam) in infants with symptomatic Type 1 spinal muscular atrophy (SMA). The data showed an estimated 91% of infants (n=58) treated with Evrysdi were alive after three years of treatment. The Evrysdi-treated infants continued to improve or maintain motor functions, including the ability to swallow, sit without support, stand with support and walk while holding on, between two and three years of treatment. Without treatment, children with Type 1 SMA are never able to sit without support. The study also showed overall continued reductions in serious adverse events (SAEs) and hospitalizations over time.
The FIREFISH study evaluated the efficacy and safety of Evrysdi in infants aged 1-7 months at the time of enrollment with Type 1 SMA. The study was in two parts, with Part 1 being the dose-finding period and Part 2 evaluating the efficacy and safety at the dose selected in Part 1. The pooled population includes participants treated with Evrysdi at the approved dose for a minimum of three years. These long-term data will be presented at the 14th European Paediatric Neurology Society (EPNS) Congress, April 28 – May 2, 2022.
“These long-term results in babies treated with Evrysdi are very encouraging, with the vast majority improving or maintaining motor functions after three years. Without treatment, they would typically not survive beyond two years of age,” said Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development. “Support for the compelling efficacy of Evrysdi continues to grow for a broad range of people, including infants with one of the most severe forms of SMA.”
Infants treated with Evrysdi maintained or continued to improve in their ability to sit without support between 24-36 months. Among the infants with an available assessment (n=48) treated with Evrysdi, 32 infants maintained and 4 gained the ability to sit without support for at least 5 seconds since month 24, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). In addition, 20 infants maintained and 15 gained the ability to sit without support for at least 30 seconds. No infant who gained the ability to sit without support lost this ability after three years of treatment. The majority of infants treated with Evrysdi maintained the ability to feed orally and swallow up to month 36.
Most of the infants treated with Evrysdi continued to improve or maintain measures of the Hammersmith Infant Neurological Examination 2 (HINE-2) between 24-36 months, including being able to hold their heads upright (36 maintained, 3 gained and none lost the ability since month 24), pivot while sitting (15 maintained, 11 gained and none lost the ability), stand with support (6 maintained, 5 gained and 1 lost the ability) and walk while holding on (1 maintained, 2 gained and none lost the ability).
The most common adverse events (AEs) were pyrexia (60%), upper respiratory tract infection (57%), pneumonia (43%), constipation (26%), nasopharyngitis (24%), diarrhea (21%), rhinitis (19%), vomiting (19%) and cough (17%). The most common SAEs were pneumonia (36%), respiratory distress (10%), viral pneumonia (9%), acute respiratory failure (5%) and respiratory failure (5%). The rate of AEs, including pneumonia, continued to decrease over time. The rate of SAEs similarly decreased, with a reduction of approximately 50% after each 12-month treatment period and a 78% reduction between the first and third year of treatment. All AEs and SAEs reported were reflective of the underlying disease and there were no treatment-related AEs leading to withdrawal or treatment discontinuation. The rate of hospitalizations decreased from 1.24 hospitalizations per patient year over 12 months to 0.70 hospitalizations over 36 months. No additional deaths have occurred since the primary analysis of FIREFISH, up to the data cut-off of this analysis (November 23, 2021).
Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.
About Evrysdi® (risdiplam)
Evrysdi is a survival motor neuron 2 (SMN2) splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to survival motor neuron (SMN) protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.
Evrysdi is designed to treat SMA by increasing and sustaining the production of SMN protein in the central nervous system (CNS) and peripheral tissues as demonstrated in animal models. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.
Evrysdi was granted PRIME designation by the European Medicines Agency (EMA) in 2018 and Orphan Drug Designation by the U.S. Food and Drug Administration in 2017. In 2021 Evrysdi was awarded Drug Discovery of the Year by the British Pharmacological Society as well as the Society for Medicines Research award for Drug Discovery. Evrysdi is currently approved in 76 countries and the dossier is under review in a further 29 countries.
Evrysdi is currently being evaluated in five multicenter trials in people with SMA:
- FIREFISH (NCT02913482) – an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety profile of Evrysdi in infants and determining the dose for Part 2. Part 2 is a pivotal, single-arm study of Evrysdi in 41 infants with Type 1 SMA treated for two years, followed by an open-label extension. Enrollment for Part 2 was completed in November 2018. The primary objective of Part 2 was to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed by the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) (defined as sitting without support for 5 seconds). The study met its primary endpoint.
- SUNFISH (NCT02908685) – SUNFISH is a two-part, double-blind, placebo-controlled pivotal study in people aged 2-25 years with Types 2 or 3 SMA. Part 1 (n=51) determined the dose for the confirmatory Part 2. Part 2 (n=180) evaluated motor function using the total score of Motor Function Measure 32 (MFM-32) at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint.
- JEWELFISH (NCT03032172) – an open-label exploratory trial designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in people with SMA aged 6 months to 60 years who received other investigational or approved SMA therapies for at least 90 days prior to receiving Evrysdi. The study has completed recruitment (n=174).
- RAINBOWFISH (NCT03779334) – an open-label, single-arm, multicenter study, investigating the efficacy, safety, PK and PD of Evrysdi in babies (~n=25), from birth to six weeks of age (at first dose) with genetically diagnosed SMA who are not yet presenting with symptoms. The study is fully enrolled.
- MANATEE (NCT05115110) – a global phase 2/3 clinical study to evaluate the safety and efficacy of GYM329 (RO7204239), an anti-myostatin molecule targeting muscle growth, in combination with Evrysdi for the treatment of SMA in patients 2-10 years of age. The FDA Office of Orphan Products Development granted GYM329 Orphan Drug Designation for the treatment of patients with SMA in December 2021. The study is commencing recruitment in Q2 2022.
What is Evrysdi?
Evrysdi is a prescription medicine used to treat spinal muscular atrophy (SMA) in adults and children 2 months of age and older.
It is not known if Evrysdi is safe and effective in children under 2 months of age.
- https://www.evrysdi.com/
- Please see the full Prescribing Information for additional Important Safety Information.
For additional information about the company, please visit http://www.gene.com.
Genentech's Evrysdi shows long-term improvements in spinal muscular atrophy patients
Apr. 29, 2022 9:59 AM ET
By: Jonathan Block, SA News Editor
- Evrysdi (risdiplam), a treatment for spinal muscular atrophy from Roche (OTCQX:RHHBY) unit Genentech, demonstrated improvements in survival and motor functions after three years.
- https://seekingalpha.com/news/3829435-genentech-roche-evrysdi-shows-long-term-improvements-in-spinal-muscular-atrophy-patients
- https://seekingalpha.com/symbol/RHHBY
- https://www.evrysdi.com/
- https://www.gene.com/
tirzepatide
Lilly's tirzepatide delivered up to 22.5% weight loss in adults with obesity or overweight in SURMOUNT-1
April 28, 2022Download PDF
Participants taking tirzepatide lost up to 52 lb. (24 kg) in this 72-week phase 3 study
63% of participants taking tirzepatide 15 mg achieved at least 20% body weight reductions as a key secondary endpoint
INDIANAPOLIS, April 28, 2022 /PRNewswire/ -- Tirzepatide (5 mg, 10 mg, 15 mg) achieved superior weight loss compared to placebo at 72 weeks of treatment in topline results from Eli Lilly and Company's (NYSE: LLY) SURMOUNT-1 clinical trial, with participants losing up to 22.5% (52 lb. or 24 kg) of their body weight for the efficacy estimandi. This study enrolled 2,539 participants and was the first phase 3 global registration trial evaluating the efficacy and safety of tirzepatide in adults with obesity, or overweight with at least one comorbidity, who do not have diabetes. Tirzepatide met both co-primary endpoints of superior mean percent change in body weight from baseline and greater percentage of participants achieving body weight reductions of at least 5% compared to placebo for both estimandsii. The study also achieved all key secondary endpoints at 72 weeks.
For the efficacy estimand, participants taking tirzepatide achieved average weight reductions of 16.0% (35 lb. or 16 kg on 5 mg), 21.4% (49 lb. or 22 kg on 10 mg) and 22.5% (52 lb. or 24 kg on 15 mg), compared to placebo (2.4%, 5 lb. or 2 kg). Additionally, 89% (5 mg) and 96% (10 mg and 15 mg) of people taking tirzepatide achieved at least 5% body weight reductions compared to 28% of those taking placebo.
In a key secondary endpoint, 55% (10 mg) and 63% (15 mg) of people taking tirzepatide achieved at least 20% body weight reductions compared to 1.3% of those taking placebo. In an additional secondary endpoint not controlled for type 1 error, 32% of participants taking tirzepatide 5 mg achieved at least 20% body weight reductions. The mean baseline body weight of participants was 231 lb. (105 kg).
"Obesity is a chronic disease that often does not receive the same standard of care as other conditions, despite its impact on physical, psychological and metabolic health, which can include increased risk of hypertension, heart disease, cancer and decreased survival," said Louis J. Aronne, MD, FACP, DABOM, director of the Comprehensive Weight Control Center and the Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, obesity expert at NewYork-Presbyterian/Weill Cornell Medical Center and Investigator of SURMOUNT-1. "Tirzepatide delivered impressive body weight reductions in SURMOUNT-1, which could represent an important step forward for helping the patient and physician partnership treat this complex disease."
For the treatment-regimen estimandiii, results showed:
- Average body weight reductions: 15.0% (5 mg), 19.5% (10 mg), 20.9% (15 mg), 3.1% (placebo)
- Percentage of participants achieving body weight reductions of ≥5%: 85% (5 mg), 89% (10 mg), 91% (15 mg), 35% (placebo)
- Percentage of participants achieving body weight reductions of ≥20%: 30% (5 mg, not controlled for type 1 error), 50% (10 mg), 57% (15 mg), 3.1% (placebo)
The overall safety and tolerability profile of tirzepatide was similar to other incretin-based therapies approved for the treatment of obesity. The most commonly reported adverse events were gastrointestinal-related and generally mild to moderate in severity, usually occurring during the dose escalation period. For those treated with tirzepatide (5 mg, 10 mg and 15 mg, respectively), nausea (24.6%, 33.3%, 31.0%), diarrhea (18.7%, 21.2%, 23.0%), vomiting (8.3%, 10.7%, 12.2%) and constipation (16.8%, 17.1%, 11.7%) were more frequently experienced compared to placebo (9.5% [nausea], 7.3% [diarrhea], 1.7% [vomiting], 5.8% [constipation]).
Treatment discontinuation rates due to adverse events were 4.3% (5 mg), 7.1% (10 mg), 6.2% (15 mg) and 2.6% (placebo). The overall treatment discontinuation rates were 14.3% (5 mg), 16.4% (10 mg), 15.1% (15 mg) and 26.4% (placebo).
Participants who had pre-diabetes at study commencement will remain enrolled in SURMOUNT-1 for an additional 104 weeks of treatment following the initial 72-week completion date to evaluate the impact on body weight and the potential differences in progression to type 2 diabetes at three years of treatment with tirzepatide compared to placebo.
"Tirzepatide is the first investigational medicine to deliver more than 20 percent weight loss on average in a phase 3 study, reinforcing our confidence in its potential to help people living with obesity," said Jeff Emmick, MD, Ph.D., vice president, product development, Lilly. "Obesity is a chronic disease that requires effective treatment options, and Lilly is working relentlessly to support people with obesity and modernize how this disease is approached. We're proud to research and develop potentially innovative treatments like tirzepatide, which helped nearly two thirds of participants on the highest dose reduce their body weight by at least 20 percent in SURMOUNT-1."
Tirzepatide is a novel investigational once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist, representing a new class of medicines being studied for the treatment of obesity. Tirzepatide is a single peptide that activates the body's receptors for GIP and GLP-1, two natural incretin hormones. Obesity is a chronic, progressive disease caused by disruptions in the mechanisms that control body weight, often leading to an increase in food intake and/or a decrease in energy expenditure. These disruptions are multifactorial and can be related to genetic, developmental, behavioral, environmental and social factors. To learn more, visit Lilly.com/obesity.
Lilly will continue to evaluate the SURMOUNT-1 results, which will be presented at an upcoming medical meeting and submitted to a peer-reviewed journal. Additional studies are ongoing for tirzepatide as a potential treatment for obesity or overweight.
About tirzepatide
Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1 receptor agonists. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with GLP-1 receptor agonism, may result in greater effects on markers of metabolic dysregulation such as body weight, glucose and lipids. Tirzepatide is in phase 3 development for adults with obesity or overweight with weight-related comorbidity and is currently under regulatory review as a treatment for adults with type 2 diabetes. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction (HFpEF). Studies of tirzepatide in obstructive sleep apnea (OSA) and in morbidity/mortality in obesity are planned as well.
About SURMOUNT-1 and the SURMOUNT clinical trial program
SURMOUNT-1 (NCT04184622) is a multi-center, randomized, double-blind, parallel, placebo-controlled trial comparing the efficacy and safety of tirzepatide 5 mg, 10 mg and 15 mg to placebo as an adjunct to a reduced-calorie diet and increased physical activity in adults without type 2 diabetes who have obesity, or overweight with at least one of the following comorbidities: hypertension, dyslipidemia, obstructive sleep apnea or cardiovascular disease. The trial randomized 2,539 participants across the U.S., Argentina, Brazil, China, India, Japan, Mexico, Russia and Taiwan in a 1:1:1:1 ratio to receive either tirzepatide 5 mg, 10 mg or 15 mg or placebo. The co-primary objectives of the study were to demonstrate that tirzepatide 10 mg and/or 15 mg is superior in percentage of body weight reductions from baseline and percentage of participants achieving ≥5% body weight reduction at 72 weeks compared to placebo. Participants who had pre-diabetes at study commencement will remain enrolled in SURMOUNT-1 for an additional 104 weeks of treatment following the initial 72-week completion date to evaluate the impact on body weight and potential differences in progression to type 2 diabetes at three years of treatment with tirzepatide compared to placebo.
All participants in the tirzepatide treatment arms started the study at a dose of tirzepatide 2.5 mg once-weekly and then increased the dose in a step-wise approach at four-week intervals to their final randomized maintenance dose of 5 mg (via a 2.5 mg step), 10 mg (via steps at 2.5 mg, 5 mg and 7.5 mg) or 15 mg (via steps at 2.5 mg, 5 mg, 7.5 mg, 10 mg and 12.5 mg).
The SURMOUNT phase 3 global clinical development program for tirzepatide began in late 2019 and has enrolled more than 5,000 people with obesity or overweight across six clinical trials, four of which are global studies. Results from SURMOUNT-2, -3, and -4 are anticipated in 2023.
To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY
View original content to download multimedia:https://www.prnewswire.com/news-releases/lillys-tirzepatide-delivered-up-to-22-5-weight-loss-in-adults-with-obesity-or-overweight-in-surmount-1--301534871.html
SOURCE Eli Lilly and Company
Lilly's tirzepatide shows weight loss benefit in adults without diabetes
Apr. 28, 2022 9:28 AM ET Eli Lilly and Company (LLY)NVO
By: Jonathan Block, SA News Editor4 Comments
- Eli Lilly's (NYSE:LLY) tirzepatide has demonstrated a significant weight loss benefit in individuals without diabetes in a late-stage trial.
- https://seekingalpha.com/news/3828625-eli-lilly-tirzepatide-shows-weight-loss-benefit-in-adults-without-diabetes
- https://seekingalpha.com/symbol/LLY
- https://www.lilly.com/
biotecMAX™ Feb/Mar/APR 2022 Insight
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu granted Breakthrough Therapy Designation in the US for patients with HER2-low metastatic breast cancer
PUBLISHED27 April 2022
27 April 2022 07:00 BST
Based on DESTINY-Breast04 results where AstraZeneca and Daiichi Sankyo’s Enhertu demonstrated a significant improvement in both progression-free survival and overall survival
Enhertu has now been granted five Breakthrough Therapy Designations, including three in breast cancer and one in both lung and gastric cancers
AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has been granted Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The Food and Drug Administration’s (FDA) BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.
Up to half of all patients with breast cancer have tumours with a HER2 immunohistochemistry (IHC) score of 1+, or 2+ in combination with a negative in-situ hybridisation (ISH) test, a level of HER2 expression not currently eligible for HER2-targeted therapy.1-4 Low HER2 expression occurs in both HR-positive and HR-negative disease.5
HER2 testing is routinely used to determine appropriate treatment options for patients with metastatic breast cancer. Targeting the lower range of expression in the HER2 spectrum may offer another approach to delay disease progression and extend survival in patients with metastatic breast cancer.6 Currently chemotherapy remains the only treatment option for patients with HR-positive tumours following progression on endocrine (hormone) therapy.7 Few targeted options are available for those who are HR-negative.8
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: “Today’s news is a significant validation of the potential we see for the historic DESTINY-Breast04 trial to enable a paradigm shift in how breast cancer is classified by targeting the full spectrum of HER2 expression. Enhertu continues to show transformative potential, and this milestone represents an important advance for patients with HER2-low metastatic breast cancer who are in urgent need of new treatment options and better outcomes.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo said: “Historically, only patients with HER2-positive metastatic breast cancer were shown to benefit from HER2-directed therapy. DESTINY-Breast04, in which Enhertu showed a clinically meaningful survival benefit in patients with HER2-low metastatic breast cancer, is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients. This Breakthrough Therapy Designation acknowledges the potential of Enhertu to fulfil an unmet medical need and we look forward to working closely with the FDA to bring the first HER2-directed therapy to patients with metastatic breast cancer whose tumours have lower levels of HER2 expression.”
The FDA granted the BTD based on data from the pivotal DESTINY-Breast04 Phase III trial which reported positive high-level results in February 2022. In the trial, Enhertu demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) in patients with HER2-low unresectable and/or metastatic breast cancer in all randomised patients with HR-positive and HR-negative disease versus physician’s choice of chemotherapy, which is the current standard of care. The safety profile of Enhertu was consistent with previous clinical trials with no new safety concerns identified. The data will be presented at an upcoming medical meeting.
This is the third BTD for Enhertu in breast cancer. Enhertu previously received BTD’s for the treatment of second-line HER2-positive metastatic breast cancer in 2021 and later-line HER2-positive metastatic breast cancer in 2017. Two additional BTD’s for Enhertu were granted in 2020 for HER2-mutant metastatic non-small cell lung cancer (NSCLC) and HER2-positive metastatic gastric cancer.
DESTINY-Breast04
DESTINY-Breast04 is a global, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive (n=480) or HR-negative (n=60) HER2-low unresectable and/or metastatic breast cancer previously treated with one or two prior lines of chemotherapy. Patients were randomised 2:1 to receive either Enhertu or chemotherapy.
The primary endpoint of DESTINY-Breast04 is PFS in patients with HR-positive disease based on blinded independent central review (BICR). Key secondary endpoints include PFS based on BICR in all randomised patients (HR-positive and HR-negative disease), OS in patients with HR-positive disease and OS in all randomised patients (HR-positive and HR-negative disease). Other secondary endpoints include PFS based on BICR and investigator assessment, duration of response based on BICR and safety.
DESTINY-Breast04 enrolled approximately 540 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu gets FDA breakthrough therapy tag for breast cancer subtype
Apr. 27, 2022 6:20 AM ET Daiichi Sankyo Company, Limited (DSNKY), AZN DSKYF By: Ravikash, SA News Editor1 Comment
- The Food and Drug Administration (FDA) granted breakthrough therapy designation to AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo's (OTCPK:DSKYF) (OTCPK:DSNKY) Enhertu to treat certain patients with breast cancer.
- https://seekingalpha.com/news/3827402-astrazeneca-daiichi-sankyos-enhertu-gets-fda-breakthrough-therapy-tag-for-breast-cancer-subtype
- https://seekingalpha.com/symbol/DSKYF
- https://seekingalpha.com/symbol/DSNKY
- https://seekingalpha.com/symbol/AZN
- https://www.enhertu.com/en/
- https://www.astrazeneca.com/
BRUKINSA (zanubrutinib)
BeiGene Announces BRUKINSA (zanubrutinib) Approval in Uruguay in Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Waldenström’s Macroglobulinemia
Apr 28, 2022 7:00 AM
BRUKINSA is now available in four countries in Latin America, following previous approvals in Brazil, Chile, and Ecuador
Under an exclusive distribution agreement, Adium will commercialize BRUKINSA in Latin America
MONTEVIDEO, Uruguay & CAMBRIDGE, Mass & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, today announced that the BTK inhibitor BRUKINSA (zanubrutinib) has been approved in Uruguay for the treatment of adult patients with previously treated mantle cell lymphoma (MCL), relapsed or refractory marginal zone lymphoma (MZL), and Waldenström’s macroglobulinemia (WM). BeiGene and Adium entered into an exclusive distribution agreement for Adium to commercialize BRUKINSA in Latin America.
“Tolerability of treatments for B-cell malignancies is an important consideration with BTK inhibition, and BRUKINSA was designed with that in mind to maximize BTK occupancy and minimize off-target binding. Today, we have a new treatment option for patients with MCL, MZL and WM in Uruguay, providing hope for improved treatment outcomes,” said Dr. Karina Cicinelli, Corporate Medical Director at Adium.
“We are proud of the progress BeiGene has made in Latin America over the past year, with this approval in three indications in Uruguay following recent launches in Brazil, Chile and Ecuador. With Adium’s established commercial presence in Latin America, we hope patients with MCL, MZL, and WM will soon have access to this important treatment option,” commented Eduardo Molinari, Senior Director of New Market Development in Latin America at BeiGene.
About BRUKINSA
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.
BRUKINSA has previously been approved for three indications in the United States: for the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (Nov. 2019)*; for the treatment of adult patients with Waldenström’s macroglobulinemia (WM) (Aug. 2021); and for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen (Sept. 2021)*.
BRUKINSA is supported by a broad clinical program which includes more than 3,900 subjects in 35 trials across 28 markets. To date, BRUKINSA has received more than 20 approvals covering more than 40 countries and regions, including the United States, China, the EU and Great Britain, Canada, Australia and additional international markets. Currently, more than 40 additional regulatory submissions are in review around the world.
* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.
Please see full U.S. Prescribing Information at www.beigene.com/PDF/BRUKINSAUSPI.pdf and Patient Information at www.beigene.com/PDF/BRUKINSAUSPPI.pdf.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220427006162/en/
Source: BeiGene
BeiGene Brukinsa gets approval in Uruguay to treat certain blood cancers
Apr. 28, 2022 8:51 AM ET
By: Ravikash, SA News Editor
- BeiGene (NASDAQ:BGNE) said its medicine Brukinsa was approved in Uruguay to treat adult patients with previously treated mantle cell lymphoma (MCL), relapsed or refractory marginal zone lymphoma (MZL), and Waldenström's macroglobulinemia (WM).
- https://seekingalpha.com/news/3828582-beigene-brukinsa-gets-approval-in-uruguay-to-treat-certain-blood-cancers
- https://seekingalpha.com/symbol/BGNE
- https://www.brukinsa.com/
- https://www.beigene.com/
Niraparib and ZYTIGA® (abiraterone acetate)
Janssen Submits Marketing Authorisation Application to EMA Seeking Approval of Niraparib and Abiraterone Acetate Dual Action Tablet Plus Prednisone for the Treatment of Patients with HRR Gene-Mutated Metastatic Castration Resistant Prostate Cancer
The submission to the European Medicines Agency is based on results from the Phase 3 MAGNITUDE study evaluating niraparib in combination with abiraterone acetate plus prednisonefor the treatment of patients with mCRPC who are positive for HRR gene alterations.1
April 28, 2022 08:52 AM Eastern Daylight Time
BEERSE, Belgium--(BUSINESS WIRE)--The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the submission of a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) seeking approval of niraparib in combination with abiraterone acetate, in the form of a dual action tablet (DAT)* plus prednisolone, for the treatment of patients with prostate cancer who have progressed to metastatic castration-resistant prostate cancer (mCRPC) and are positive for homologous recombination repair (HRR)+ gene alterations. When approved by the European Commission, niraparib in combination with AAP will be the first dual action tablet formulation in the European Union specifically targeting HRR gene alterations in mCRPC.
The combination of niraparib, a PARP (poly adenosine diphosphate-ribose polymerase) inhibitor, and abiraterone acetate, a CYP17 inhibitor, targets two oncogenic drivers in patients with mCRPC, AR-axis and HRR gene alterations. The DAT formulation is also intended to be more convenient for patients, and thus aims to improve treatment compliance. Prostate cancer is one of the most common cancers in Europe with approximately 473,000 patients diagnosed in 2020.2 Up to approximately 30% of patients with mCRPC have HRR gene alterations which are associated with a worse prognosis compared to patients without HRR gene alterations.1
“People with prostate cancer harbouring BRCA alterations face a more aggressive form of disease with worse outcomes and faster progression, sadly leading to a shorter life expectancy,” commented Professor Gerhardt Attard=, Primary Study Investigator and Clinician Scientist and Team Leader at University College London Cancer Institute. “This submission is an important step towards improving the outcomes for people with metastatic prostate cancer harbouring BRCA alterations using a targeted therapy that significantly delays the time to their cancer progressing.”
The EU MAA is supported by data from the MAGNITUDE study (NCT03748641), a Phase 3, randomised, double-blind, placebo-controlled, multicentre study evaluating the safety and efficacy of niraparib combined with abiraterone acetate plus prednisone (AAP) in patients with mCRPC. The study showed that at the final analysis for radiographic progression-free survival (rPFS), the treatment combination of niraparib and AAP demonstrated a statistically significant improvement in patients with HRR gene alterations as compared to placebo and AAP.1 First results from the study were presented at the American Society of Clinical Oncology – Genitourinary Cancers Symposium (ASCO GU 2022) Annual Meeting (Abstract #12). The study continues to collect data on the secondary endpoints, which include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.1
“The data supporting this submission demonstrate the benefit of niraparib in combination with AAP in patients with specific gene alterations and reinforce the importance of biomarker testing in helping to provide an individualised treatment for these patients,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Janssen Research & Development, LLC. “We are committed to advancing targeted therapeutic options for patients with prostate cancer as we build upon our deep understanding of the disease, with a focus on improving outcomes for patients.”
“The submission of niraparib in combination with AAP to the European Medicines Agency marks an important milestone in addressing specific genetic alterations in prostate cancer,” said Mathai Mammen, M.D., Ph.D., Executive Vice President, Pharmaceuticals, R&D, Johnson & Johnson. “We are determined to transform this complex disease through innovation, science and ingenuity.”
###
About Niraparib
Niraparib is an orally administered, selective poly-ADP ribose polymerase (PARP) inhibitor, that is currently being studied by Janssen for the treatment of patients with prostate cancer.1 Additional ongoing studies include the Phase 3 AMPLITUDE study evaluating the combination of niraparib and AAP in a biomarker-selected patient population with metastatic hormone-sensitive prostate cancer (mHSPC).3
In April 2016, Janssen Biotech, Inc. entered a worldwide (except Japan) collaboration and license agreement with TESARO, Inc. (acquired by GSK in 2018), for exclusive rights to niraparib in prostate cancer. In the European Union, niraparib is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy; for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy (Zejula SmPC 2021). Niraparib is currently marketed by GSK as ZEJULA®.4
About abiraterone acetate
Abiraterone acetate is an orally-administered androgen biosynthesis inhibitor. In the European Union, abiraterone acetate is indicated with prednisone or prednisolone for the treatment of newly diagnosed high risk mHSPC in adult men in combination with ADT; the treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated; and the treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel based chemotherapy regimen (ZYTIGA SmPC 2020).5
Abiraterone acetate is currently marketed by Janssen Janssen-Cilag International NV as ZYTIGA®.5
About MAGNITUDE
MAGNITUDE (NCT03748641) is a Phase 3 randomised, double-blind, placebo-controlled, multicentre clinical study evaluating the safety and efficacy of the combination of niraparib and AAP for patients with mCRPC, with or without certain HRR gene alterations. The study includes two cohorts in which patients were randomised to receive either niraparib and AAP or placebo and AAP cohorts: one cohort of patients with predefined HRR gene alterations (including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2 alterations) and one cohort of patients without HRR gene alterations. In a third, open-label cohort, all patients received the dual action tablet formulation of niraparib and AAP.1
The primary endpoint of the MAGNITUDE trial is rPFS. Secondary endpoints include time-to-initiation of cytotoxic chemotherapy, time to symptomatic progression and overall survival.1
Learn more at www.janssen.com/emea/. Follow us at www.twitter.com/JanssenEMEA for our latest news. Janssen Research & Development, LLC; Janssen-Cilag, S.A.; and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
J&J seeks approval of Zytiga/Zejula combination for prostate cancer to EMA
Apr. 28, 2022 10:13 AM ET
By: Jonathan Block, SA News Editor
- Johnson and Johnson's (NYSE:JNJ) Janssen unit has submitted a marketing authorization application to the European Medicines Agency (EMA) seeking approval of a combination of Zytiga (abiraterone acetate) and Zejula (niraparib) for prostate cancer.
- https://seekingalpha.com/news/3828664-johnson-johnson-janssen-seeks-approval-of-zytiga-zejula-combination-for-prostate-cancer-to-ema
- https://seekingalpha.com/symbol/JNJ
- https://www.zytiga.com/
- https://zejula.com/
- https://www.janssen.com/
- https://www.jnj.com/
Tremelimumab in combination with Imfinzi (durvalumab)
Tremelimumab accepted under Priority Review in the US for patients with unresectable liver cancer in combination with Imfinzi
PUBLISHED25 April 2022
25 April 2022 07:00 BST
STRIDE regimen of a single priming dose of tremelimumab added to Imfinzi is the first dual immune checkpoint blockade regimen to improve overall survival in a Phase III trial in this setting
AstraZeneca’s Biologics License Application (BLA) for tremelimumab has been accepted for Priority Review in the US, supporting the indication of a single priming dose of the anti-CTLA4 antibody added to Imfinzi (durvalumab) for the treatment of patients with unresectable hepatocellular carcinoma (HCC). A supplemental BLA (sBLA) has also been submitted for Imfinzi in this indication. This novel dose and schedule of the combination is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab).
The Prescription Drug User Fee Act date, the Food and Drug Administration (FDA) action date for their regulatory decision, is during the fourth quarter of 2022 following the use of a priority review voucher.
Liver cancer, of which HCC is the most common type, is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1,2 Approximately 26,000 people in the US present with advanced, unresectable HCC each year.3
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The HIMALAYA Phase III trial showed an unprecedented three-year overall survival in this setting with a single priming dose of tremelimumab added to Imfinzi, highlighting the potential for this regimen to improve longer-term survival outcomes. Patients with advanced liver cancer are in great need of new treatment options, and we are working closely with the FDA to bring this novel approach to patients in the US as soon as possible.”
The BLA for tremelimumab and sBLA for Imfinzi are based on final results from the HIMALAYA Phase III trial presented at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
In this trial, patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 96.02% confidence interval [CI] 0.65-0.93; p=0.0035).4 Nearly one in three (31%) patients were still alive at three years versus one in five (20%) for sorafenib.4
The safety profiles of the STRIDE regimen and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified.
Imfinzi and tremelimumab were granted Orphan Drug Designation in the US for the treatment of HCC in January 2020.
As part of its extensive clinical development programme in gastrointestinal (GI) cancers, AstraZeneca is further assessing Imfinzi across multiple liver cancer settings, including locoregional HCC (EMERALD-1, EMERALD-3) and adjuvant HCC
HIMALAYA
HIMALAYA was a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy and the STRIDE regimen, comprising a single priming dose of tremelimumab 300mg added to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy (treatment localised to the liver and surrounding tissue).
The trial was conducted in 181 centres across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint is overall survival (OS) for STRIDE versus sorafenib and key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate and progression-free survival (PFS) for STRIDE and for Imfinzi alone.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.
In the past year, Imfinzi has demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in advanced biliary tract cancer (TOPAZ-1), unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with small cell lung cancer, NSCLC, bladder cancer, several gastrointestinal cancers, ovarian cancer, endometrial cancer, and other solid tumours.
Tremelimumab
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
Beyond HIMALAYA, tremelimumab is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3), SCLC (ADRIATIC) and bladder cancer (VOLGA and NILE).
Tremelimumab is also under review by global regulatory authorities in combination with Imfinzi and chemotherapy in 1st-line metastatic NSCLC based on the results of the POSEIDON Phase III trial, which showed the addition of a short course of tremelimumab to Imfinzi plus chemotherapy improved both overall and progression-free survival compared to chemotherapy alone.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca gets FDA priority review for new dosing regimen of tremelimumab/Imfinzi in liver cancer
Apr. 25, 2022 5:42 AM ET AstraZeneca PLC (AZN)BAYZF, BAYRY
By: Ravikash, SA News Editor1 Comment
The Food and Drug Administration (FDA) granted priority review to AstraZeneca's (NASDAQ:AZN) application for a single priming dose of tremelimumab added to Imfinzi (durvalumab) to treat patients with unresectable hepatocellular carcinoma, a type of liver cancer.
https://seekingalpha.com/symbol/AZN
Ultomiris (ravulizumab-cwvz)
28 April 2022 07:00 BST
First and only long-acting C5 complement inhibitor to demonstrate clinical improvement in patients with generalised myasthenia gravis
Ultomiris showed early effect and lasting improvement in activities of daily living and has potential to reduce treatment burden with dosing every 8 weeks
Ultomiris (ravulizumab-cwvz) has been approved in the US for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease.1-5
The approval by the Food and Drug Administration (FDA) was based on positive results from the CHAMPION-MG Phase III trial, in which Ultomiris was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.1
This FDA action marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG.
gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.6 The diagnosed prevalence of gMG in the US is estimated at approximately 90,000.7
Professor James F. Howard, Jr, MD, Department of Neurology at The University of North Carolina School of Medicine and lead primary investigator in the CHAMPION-MG trial said: “Despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy.”
Samantha Masterson, Chief Executive Officer, Myasthenia Gravis Foundation of America (MGFA), said: “gMG takes a physical and emotional toll on those living with the disease. We are grateful for continued innovation and research into new treatment and dosing options to meet the needs of more patients and reduce the treatment burden. With the approval of Ultomiris, we’re excited that MG patients now have another option to consider as part of their personalised treatment strategies that may offer more convenience and improve muscle weakness.”
Marc Dunoyer, Chief Executive Officer, Alexion, said: “Since bringing forward the first complement inhibitor, we’ve continued to listen to the community and focused innovation on the needs of gMG patients. We’re proud to deliver on this commitment with today’s approval. Ultomiris, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms. As presented at the 2022 American Academy of Neurology Annual Meeting, Ultomiris has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to Soliris every two weeks.”
In the trial, the safety profile of Ultomiris was comparable to placebo and consistent with that observed in Phase III trials of Ultomiris in paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). The most common adverse reactions in patients receiving Ultomiris were upper respiratory tract infection and diarrhoea.1
Results from the CHAMPION-MG trial were recently published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting in April.
Regulatory submissions for Ultomiris for the treatment of gMG are currently under review with multiple health authorities, including in the European Union (EU) and Japan.
CHAMPION-MG
The global Phase III randomised, double-blind, placebo-controlled, multicentre 26-week trial evaluated the safety and efficacy of Ultomiris in adults with gMG. The trial enrolled 175 patients across North America, Europe, Asia-Pacific and Japan. Participants were required to have a confirmed myasthenia gravis diagnosis at least six months prior to the screening visit with a positive serologic test for anti-AChR antibodies, MG-ADL total score of at least 6 at trial entry and Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening. Patients could stay on stable standard of care medicines, with a few exceptions, for the duration of the randomised control period.13
Patients were randomised 1:1 to receive Ultomiris or placebo for a total of 26 weeks. Patients received a single weight-based loading dose on Day 1, followed by regular weight-based maintenance dosing beginning on Day 15, every eight weeks. The primary endpoint of change from baseline in the MG-ADL total score at Week 26 was assessed along with multiple secondary endpoints evaluating improvement in disease-related and quality-of-life measures.
Patients who completed the randomised control period were eligible to continue into an open-label extension period evaluating the safety and efficacy of Ultomiris, which is ongoing.
Ultomiris
Ultomiris (ravulizumab-cwvz), the first and only long-acting C5 complement inhibitor, offers immediate, complete and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose.
Ultomiris is approved in the US for the treatment of certain adults with gMG.
Ultomiris is also approved in the US, EU and Japan for the treatment of certain adults and children with PNH.
Additionally, Ultomiris is approved in the US, EU and Japan for certain adults and children with aHUS to inhibit complement-mediated thrombotic microangiopathy.
As part of a broad development programme, Ultomiris is being assessed for the treatment of additional haematology and neurology indications.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for nearly 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca's Ultomiris wins FDA approval for rare neuromuscular disorder
Apr. 28, 2022 6:59 AM ET
By: Ravikash, SA News Editor
The U.S. Food and Drug Administration approved AstraZeneca's (NASDAQ:AZN) Ultomiris to treat adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.
- https://seekingalpha.com/news/3828408-astrazenecas-ultomiris-wins-fda-approval-for-rare-neuromuscular-disorder
- https://seekingalpha.com/symbol/AZN
- https://ultomiris.com/
- https://www.astrazeneca.com/
REPATHA® (EVOLOCUMAB)
AMGEN ANNOUNCES RESULTS FROM TWO OPEN LABEL EXTENSION STUDIES OF REPATHA® (EVOLOCUMAB)
Studies Showed Sustained Reduction in LDL-C With no new Safety Findings
The Combined Studies Evaluated Safety and Tolerability of Repatha in More Than 6,600 Patients for Over Five Years After Completing the Phase 3 FOURIER Trial
Repatha is the Longest Studied PCSK9i
THOUSAND OAKS, Calif., April 27, 2022 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced top-line results from two Repatha® (evolocumab) open label extension (OLE) studies to the Phase 3 FOURIER cardiovascular outcomes trial. The studies were designed to assess the long-term safety and tolerability of Repatha over five years in adults with clinically evident atherosclerotic cardiovascular disease.
The FOURIER-OLE (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated – Risk-Open Label Extension) studies were composed of study 20130295 (NCT02867813) with 5,035 patients enrolled in Eastern Europe and the United States and study 20160250 (NCT03080935) with 1,600 patients enrolled in Western Europe. Both studies showed that Repatha, administered at 140 mg every two weeks or 420 mg monthly, was safe and well-tolerated. In the OLE studies, patients received Repatha for approximately 5 years, with some patients receiving Repatha for up to 8 1/2 years in aggregate across the FOURIER and OLE studies. No new long-term safety findings were observed.
In addition, medically significant and sustained reduction in low-density lipoprotein cholesterol (LDL-C) levels were observed, with more than 85 percent of patients achieving an LDL-C level of <40 mg/dL during the OLE period.
"The combined results from these studies reinforce the well-established safety profile of Repatha with long-term use in lowering LDL-C," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "As the PCSK9i leader, with more than one million patients worldwide who have received Repatha, we are extremely encouraged by the sustained benefit of this effective medicine for patients with cardiovascular disease who still struggle to get their LDL-C level below recommended goals."
Other study measures included exploratory analyses of non-high-density lipoprotein cholesterol, apolipoprotein B, total cholesterol, Lipoprotein(a), triglycerides, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, and apolipoprotein A-1 levels, as well as cardiovascular events of interest.
Detailed study results will be shared with regulatory authorities and submitted for presentation at an upcoming medical congress later this year. Prolonged LDL-C reduction with Repatha is also being studied in the ongoing VESALIUS-CV (NCT03872401) outcomes trial.
Repatha® Cardiovascular Open-Label Extension (FOURIER-OLE) Study Design
FOURIER (20110118) was a randomized placebo-controlled study of evolocumab, in patients with clinically evident atherosclerotic CVD on stable effective statin therapy. FOURIER-OLE (Further cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated – Risk-Open Label Extension) were multicenter, open-label extension (OLE) studies designed to assess the extended long-term safety of evolocumab in subjects who completed the FOURIER study (20110118). The FOURIER-OLE is composed of studies 20130295 and 20160250, which enrolled 5,035 and 1,600 subjects who completed FOURIER study (20110118) to receive open-label evolocumab and were followed up for a median of 5 and 4.6 years, respectively.
PROFICIO Program
FOURIER is part of Amgen's PROFICIO (Program to Reduce LDL-C and cardiovascular Outcomes Following Inhibition of PCSK9 In different pOpulations) program of clinical studies investigating the impact of Repatha® on LDL-C and CVD across multiple populations at high CV risk, including those managed by statins, statin-intolerant patients, those with genetic disorders and patients with atherosclerosis. To date, the PROFICIO program consists of 36 trials including more than 38,000 patients worldwide.
For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
About Repatha® (evolocumab)
Repatha® is a human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Repatha® binds to PCSK9 and inhibits circulating PCSK9 from binding to the low-density lipoprotein (LDL) receptor (LDLR), preventing PCSK9-mediated LDLR degradation and permitting LDLR to recycle back to the liver cell surface. By inhibiting the binding of PCSK9 to LDLR, Repatha® increases the number of LDLRs available to clear LDL from the blood, thereby lowering LDL-C levels.
Repatha® is approved in more than 75 countries, including the U.S., Japan, Canada and in all 28 countries that are members of the European Union. Applications in other countries are pending.
INDICATIONS
Repatha® is indicated:
- In adults with established cardiovascular disease to reduce the risk of myocardial infarction, stroke, and coronary revascularization
- As an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDLC)-lowering therapies, in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce LDL-C
- As an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged 10 years and older with HeFH, to reduce LDL-C
- As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), to reduce LDL-C
The safety and effectiveness of Repatha® have not been established in pediatric patients with HeFH or HoFH who are younger than 10 years old or in pediatric patients with other types of hyperlipidemia.
Immunogenicity: Repatha® is a human monoclonal antibody. As with all therapeutic proteins, there is potential for immunogenicity with Repatha®.Please contact Amgen Medinfo at 800-77-AMGEN (800-772-6436) or 844-REPATHA (844-737-2842) regarding Repatha® availability or find more information, including full Prescribing Information, at www.amgen.com and www.Repatha.com.
View original content to download multimedia:https://www.prnewswire.com/news-releases/amgen-announces-results-from-two-open-label-extension-studies-of-repatha-evolocumab-301534228.html
SOURCE Amgen
Amgen's Repatha sustains reduction in bad cholesterol as per long term data from 2 studies
Apr. 27, 2022 9:48 AM ET
By: Ravikash, SA News Editor2 Comments
Amgen (NASDAQ:AMGN) said data from two studies showed that its drug Repatha sustained reduction in 'bad' cholesterol.
https://seekingalpha.com/symbol/AMGN
Veklury® (Remdesivir)
April 24, 2022
Several New Studies Presented at ECCMIC 2022 Confirm Veklury® (Remdesivir) Activity in Treating COVID-19
-- Real-World Evidence from More than 850,000 Hospitalized Patients Provides Clinical Insights on the Use of Veklury (Remdesivir) as Stand of Care COVID-19 Treatment --
-- New Post-hoc Analysis of Non-Hospitalized COVID-19 Patients in the Phase 3 PINETREE Study Demonstrates Veklury Treatment Initiated Within 5 Days of Symptoms Reduced Risk for Hospitalization by 90% --
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced findings from two studies, which provide further insights on the use of Veklury® (remdesivir) for the treatment of hospitalized and non-hospitalized patients with COVID-19. The first study is a retrospective observational analysis of the real-world treatment data from the Premier Healthcare Database consisting of 853,219 patients hospitalized with COVID-19 across the United States. This analysis found that more than 50% of hospitalized COVID-19 patients received Veklury, predominantly in combination with other therapies. An oral presentation of this real-world data analysis will be given on April 25 at 11 a.m. Western European Summer Time in Hall P at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022). A separate study, which is a new post-hoc analysis of data from the Phase 3 PINETREE study, demonstrated that use of Veklury within five days of symptom onset or between 5 to 7 days of symptom onset reduced hospitalizations in patients at high risk for severe COVID-19 disease. This post-hoc analysis was presented as a poster (#L0447) at ECCMID.
The observational analysis of real-world data also found that as the pandemic progressed, initiation of Veklury within two days of hospitalization increased from 41% to 91% between May 2020 and December 2021. During this period, as new variants arose and disease severity fluctuated, median hospital length of stay (LOS) decreased from seven to six days with the greatest benefit in invasive mechanical ventilation/ ECMO patients (15 to 11 days). While ICU use decreased from 34% to 27%, with the greatest benefit in high-flow oxygen/non-invasive ventilation (66% to 52%), overall ICU LOS remained the same. Overall mortality rates remained stable at 16%, with the greatest decline over time in patients on low-flow supplemental oxygen (15% to 12%). These results confirm Veklury’s position as a foundational treatment for hospitalized patients with COVID-19 and signify the need to treat patients early before they become more severely ill with COVID-19.
“In a pandemic, real world analysis has a particularly important role in helping us understand how treatment choices are evolving over time as we work to discover the most effective treatment options for patients. We've long understood that antivirals work optimally for respiratory viruses when they are given as early as possible, without delay. This data confirms that antiviral treatment is now initiated sooner in hospitalizations and that throughout the pandemic, remdesivir has remained the foundation for hospitalized patients with COVID-19,” said Robert L. Gottlieb, MD, PhD, Baylor University Medical Center and Baylor Scott & White Research Institute. “Additionally, as healthcare providers' experience and confidence in COVID-19 therapeutic options has increased, so too has the use of therapeutic combinations, reflecting the incremental incorporation of evidence-based therapies.”
The new post-hoc analysis from a Phase 3 double-blind, placebo-controlled trial (PINETREE) demonstrating that a three-day course of Veklury treatment significantly reduced the risk of hospitalization was also presented at ECCMID. The analysis assessed the variability of treatment effect with Veklury by time of symptom onset and number of baseline risk factors. The study concluded that Veklury reduced hospitalizations in patients at high risk for severe COVID-19 disease when initiated anytime within a 7-day window from symptom onset. As expected with antiviral therapy, the benefit was modestly greater the sooner Veklury was administered. Patients treated with Veklury within five days of symptom onset had a 90% reduced risk for hospitalization. Additionally, patients who received Veklury after five 5 days of symptom onset experienced an 81% reduction in risk of hospitalization. This new analysis builds on the previously presented primary endpoint analysis, in which Veklury demonstrated a statistically significant 87% reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) p=0.008); no deaths occurred in either arm of the study through the primary endpoint.
“The data presented at ECCMID, not only underscore Veklury as the antiviral standard of care for COVID-19 treatment in hospitalized patients, but they also further emphasize that patients can benefit from Veklury when it’s given up to seven days after the onset of symptoms and that the benefit is greater the sooner it is administered,” said Frank Duff, Senior Vice President, Virology Therapeutic Head, Gilead Sciences. “As the pandemic has progressed and the utility of other treatments against new variants has shifted, we are proud that Veklury has remained the foundation for patients hospitalized with COVID-19.”
Gilead presented two additional studies from the company’s COVID-19 clinical and real-world evidence programs at the conference.
- Data from the CARAVAN study evaluated safety, pharmacokinetic, virologic, and clinical outcomes of Veklury treatment in pediatric patients who were 28 days of age and older. The interim analysis of Veklury in pediatric patients hospitalized with COVID-19 with ages ranging from 28 days to less than 18 years demonstrated that Veklury was generally well tolerated, with a high proportion of participants showing clinical improvement and recovery. Overall, no new safety findings for Veklury were noted. In the study, 75% and 85% showed clinical improvement (≥2 point increase on the ordinal scale) at Day 10 and last assessment, respectively, while 60% and 83% were discharged by Day 10 and Day 30, respectively. Overall, 38 patients (72%) experienced AEs, with 11 patients (21%) experiencing serious adverse events (SAEs) that were determined not to be study-drug related, including 3 participant deaths which were consistent with the patients’ underlying medical condition prior to study entry or with COVID-19 disease during hospitalization.
- A real-world evidence analysis evaluated data from 2,310 patients hospitalized with COVID-19 who had previously undergone kidney transplantation. The analysis found that in this patient population, overall mortality was comparable to the general population hospitalized with COVID-19, but markedly increased for those with diminished renal function, comorbidities, and higher oxygen requirements upon admission. Insights from this study help inform clinical decision-making in the context of management of kidney transplant patients and other solid-organ transplant recipients, alike.
About Veklury
Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is a foundation for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. Veklury has an established safety profile and minimal drug interactions in diverse populations. At this time, more than half of patients hospitalized with COVID-19 in the United States are treated with Veklury. It can help reduce disease progression across a spectrum of disease severity and enable patients to recover faster, freeing up limited hospital resources and saving healthcare systems money.
Veklury was approved by the FDA in October 2020, for adults and pediatric patients 12 years of age and older and weighing at least 40 kg for the treatment of COVID-19 requiring hospitalization. In January 2022, the FDA approved a supplemental NDA to expand the indication to non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. This allows for Veklury to be administered in qualified outpatient settings that can administer daily intravenous (IV) infusions over three consecutive days. Veklury also has an Emergency Use Authorization (EUA) for non-hospitalized pediatric patients weighing at least 3.5 kg who are younger than 12 years of age or weighing less than 40 kg who are at high risk of disease progression, in addition to those with COVID-19 requiring hospitalization. Veklury is contraindicated in patients who are allergic to Veklury or any of its components; please see below for additional Important Safety Information for Veklury.
Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves. Veklury is a nucleotide analog that directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. In vitro laboratory testing in multiple independent studies shows that Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves, including the Omicron variant and its subvariants BA.1 and BA.2. As new SARS-CoV-2 variants of concern emerge around the world, Gilead continuously evaluates the effectiveness of Veklury against viral variants.
Veklury is approved or authorized for temporary use in approximately 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 11 million patients around the world, including more than 7 million people in 127 middle- and low-income countries through Gilead’s voluntary licensing program. These licenses currently remain royalty-free, reflecting Gilead’s existing commitment to enabling broad patient access to remdesivir.
U.S. Indication for Veklury
Veklury® (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (12 years of age and older and weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, who are:
- Hospitalized, or
- Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Veklury should only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Veklury must be administered by intravenous infusion. Veklury is contraindicated in patients who are allergic to Veklury or any of its components. For more information, please see the U.S. full Prescribing Information available at www.gilead.com.
U.S. full Prescribing Information for Veklury is available at www.gilead.com.
Veklury, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220424005046/en/
Source: Gilead Sciences, Inc.
Gilead data shows COVID drug Veklury shows benefit if given early, cuts hospitalization risk
Apr. 25, 2022 6:27 AM ET Gilead Sciences, Inc. (GILD)
By: Ravikash, SA News Editor2 Comments
Gilead Sciences (NASDAQ:GILD) reported data showing activity of its COVID-19 therapy Veklury (remdesivir) based on real-world results from over 850K patients, and a post-hoc analysis of a phase 3 trial.
https://seekingalpha.com/symbol/GILD
April 25, 2022
Veklury® (Remdesivir) is First and Only Approved Treatment for Pediatric Patients Under 12 Years of Age with COVID-19
-- Approval is Supported by Phase 2/3 Data Demonstrating the Safety and Tolerability Profile and Clinical Improvement Outcome in Hospitalized Pediatric Patients Treated with Veklury --
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for Veklury® (remdesivir) for the treatment of pediatric patients who are older than 28 days, weighing at least 3 kg, and are either hospitalized with COVID-19 or have mild-to-moderate COVID-19 and are considered high risk for progression to severe COVID-19, including hospitalization or death. This approval follows the recent sNDA approval for Veklury for the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19.
https://seekingalpha.com/symbol/GILD
VRAYLAR® (cariprazine)
Health Canada Approves VRAYLAR® (cariprazine) for the Treatment of Bipolar l Disorder and Schizophrenia in Adults
Apr. 27, 2022 7:00 AM ET AbbVie Inc. (ABBV)
VRAYLAR® is a new atypical antipsychotic medication with partial agonist activity at central dopamine D3 receptors in addition to targeted activity at D2 and serotonin 5-HT1A and 5-HT2A receptors. 1
MONTREAL, April 27, 2022 /CNW Telbec/ - AbbVie (NYSE: ABBV), a global, research and development-based biopharmaceutical company announced today that Health Canada has approved VRAYLAR® (cariprazine) as monotherapy for the acute management of manic, mixed, and depressive episodes associated with bipolar l disorder in adults, as well as the treatment of schizophrenia in adults.1
Bipolar I disorder is a mental illness characterized by extreme mood swings that can impact an individuals' ability to think, behave and function.2 It can consist of three states which includes manic, depressive, and mixed episodes.3 While the causes of bipolar I disorder are unknown, biological factors can play a role and can be difficult to diagnose due to the wide range of symptoms.3
About VRAYLAR® (cariprazine) 1
VRAYLAR® is an oral, once daily atypical antipsychotic approved as monotherapy for the acute management of manic, mixed, and depressive episodes associated with bipolar l disorder in adults, as well as the treatment of schizophrenia in adults.
The mechanism of action of cariprazine in schizophrenia and bipolar I disorder is unknown. However, the therapeutic effect of cariprazine may be mediated through a combination of partial agonist activity at central dopamine D3, D2 and serotonin 5-HT1A receptors and antagonist activity at 5-HT2A receptors. Cariprazine forms two major metabolites, desmethyl cariprazine (DCAR) and didesmethyl cariprazine (DDCAR), that have in vitro receptor binding and functional activity profiles similar to the parent drug.
VRAYLAR® is contraindicated in patients who are hypersensitive to cariprazine or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. VRAYLAR® is also contraindicated with concomitant use with strong and moderate CYP3A4 inhibitors / inducers. Due to the slow elimination of cariprazine and its metabolites, treatment with strong and moderate CYP3A4 inhibitors must be initiated at least 2 weeks after VRAYLAR discontinuation.
VRAYLAR is being developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the U.S., Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela).
Please consult the VRAYLAR® Product Monograph at www.allergan.ca.
For more information about AbbVie, please visit us at www.abbvie.ca. Follow AbbVie Canada on Twitter, on Instagram or find us on LinkedIn.
SOURCE AbbVie Canada
https://seekingalpha.com/symbol/ABBV
VYDURA® (Rimegepant)
Pfizer and Biohaven’s VYDURA® (Rimegepant) Granted First Ever Marketing Authorization by European Commission for Both Acute Treatment of Migraine and Prophylaxis of Episodic Migraine
Wednesday, April 27, 2022 - 06:45am
NEW YORK & NEW HAVEN, Conn.--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) and Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) today announced that the European Commission (EC) has granted marketing authorization for VYDURA® (rimegepant), a calcitonin gene-related peptide (CGRP) receptor antagonist for both the acute treatment of migraine with or without aura, and prophylaxis of episodic migraine in adults who have at least four migraine attacks per month. VYDURA®, an orally disintegrating tablet, is the first medicine approved for both acute and prophylactic treatment of migraine in the European Union (EU). Migraine is a leading cause of disability worldwide with approximately one in ten people living with the condition in Europe alone. Globally, migraine disproportionately affects women by three to four times compared to men.
“There is a significant unmet need for people in the European Union living with the pain and disability caused by frequent migraines,” said Nick Lagunowich, Global President, Pfizer Internal Medicine. “The comprehensive clinical program has established VYDURA’s efficacy and safety as both an acute and preventive treatment of migraine. Studies in acute migraine demonstrated a rapid and long-lasting relief of migraine headache and other symptoms with a single dose, while the prevention study found a significant reduction in migraine attacks with every other day dosing. We have great confidence in the positive impact VYDURA could have on people living with this debilitating condition in the EU.”
Results from the Phase 3 study published in Lancet demonstrated that a single dose of rimegepant provided superior pain reduction and associated symptoms of migraine at two hours compared to placebo. The prevention study, also published in Lancet, demonstrated that rimegepant taken every other day provided superior reduction in the number of days per month with migraine in Weeks 9 –12 of the 12-week treatment period compared to placebo, that was maintained with continued dosing during the 12-month open-label extension period.
“Today’s approval marks a huge step forward for patients in Europe who are living with migraine. Migraine is often overlooked and undertreated, resulting in substantial disability with suboptimal care for patients,” commented Professor Peter Goadsby, Director of the National Institute for Health and Care Research (NIHR) Clinical Research Facility and Professor of Neurology at King’s College London. “VYDURA’s promising efficacy and favorable benefit-risk profile spark hope for people in need of new migraine treatment options. This approval has the potential to advance the standard of care for migraine in the EU and I am hopeful it will improve the quality of life for many people living with the burden of this prevalent neurological disease.”
The Marketing Authorization follows the recommendation for approval by the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) in February. The EC approval will be valid for all 27 EU member states as well as Iceland, Liechtenstein, and Norway and local reimbursement approval will follow. Assessment of the marketing authorization application by the Medicines & Healthcare products Regulatory Agency (MHRA) is underway and approval is expected to shortly follow in the United Kingdom.
About VYDURA® (rimegepant)
VYDURA® targets a key component of migraine by reversibly blocking CGRP receptors. CGRP is increased during a migraine attack, dilates blood vessels and is involved in nociceptor signaling. CGRP receptor antagonists work by reversibly blocking CGRP receptors, thereby inhibiting the biologic activity of the endogenous CGRP neuropeptide.
The Marketing Authorization for VYDURA® was based, in part, on the review of the results from three Phase 3 studies for acute treatment, a long-term, open-label safety study in acute treatment of migraine and a Phase 3 study with a 1-year open-label extension in the preventive treatment of migraine. VYDURA® is taken orally as needed, up to once daily, to stop migraine attacks or taken every other day to help prevent migraine attacks.
The most frequent adverse event in clinical trials with VYDURA® was nausea, occurring in 3% of patients compared to 1% with placebo, while hypersensitivity reactions including rash occurred in less than 1% of patients. Less than 2% of patients discontinued from VYDURA® due to adverse events. VYDURA® does not have addiction potential and was not associated with medication overuse headache or rebound headache in clinical trials, although overuse of any type of medicinal products for headache can make them worse.
VYDURA® is commercialized as Nurtec® and Nurtec® ODT outside Europe. It is commercialized in the U.S. for the acute treatment of migraine and for the preventive treatment of episodic migraine in adults, and ex-U.S. is approved for the acute treatment of migraine in Kuwait and the United Arab Emirates, and for acute treatment of migraine and preventive treatment of episodic migraine in Israel.
Earlier this year, Pfizer and Biohaven entered into an agreement for the commercialization of VYDURA®. Under the terms of the agreement, Pfizer has commercialization rights to rimegepant in markets outside the U.S. Biohaven continues to lead research and development globally and retains the U.S. market.
https://www.biohavenpharma.com/science-pipeline/cgrp/rimegepant
More information about Biohaven is available at www.biohavenpharma.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220427005213/en/
Source: Pfizer Inc.
Pfizer, Biohaven's Vydura gets approval in EU to prevent/treat migraine
Apr. 27, 2022 7:05 AM ET
Biohaven Pharmaceutical Holding Company Ltd. (BHVN), PFE
By: Ravikash, SA News Editor
- The European Commission (EC) granted marketing authorization to Biohaven Pharmaceutical (NYSE:BHVN) and Pfizer's (NYSE:PFE) Vydura (rimegepant) for the acute treatment of migraine with or without aura, and to prevent episodic migraine in adults who have at least four migraine attacks per month.
- https://seekingalpha.com/news/3827439-pfizer-biohavens-vydura-gets-approval-in-eu-to-preventtreat-migraine
- https://seekingalpha.com/symbol/BHVN
- https://www.biohavenpharma.com/science-pipeline/cgrp/rimegepant
- https://seekingalpha.com/symbol/PFE
- https://www.biohavenpharma.com/science-pipeline/cgrp/rimegepant
- https://www.nurtec.com/
RETEVMO® (selpercatinib)
Retsevmo Shareselpercatinib
On 22 April 2022, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for the medicinal product Retsevmo. The marketing authorisation holder for this medicinal product is Eli Lilly Nederland B.V.
The CHMP adopted an extension to an existing indication as follows:1
Retsevmo as monotherapy is indicated for the treatment of adults with advanced RET fusion positive non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitorwho require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
For information, the full indication for Retsevmo will therefore be as follows:
Retsevmo as monotherapy is indicated for the treatment of adults with:
- advanced RET fusion‑positive non‑small cell lung cancer (NSCLC) not previously treated with a RETinhibitor
- advanced RET fusion‑positive thyroid cancer who require systemic therapy following prior treatment with sorafenib and/or lenvatinib
Retsevmo as monotherapy is indicated for the treatment of adults and adolescents 12 years and older with advanced RET‑mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib.
Detailed recommendations for the use of this product will be described in the updated summary of product characteristics (SmPC), which will be published in the revised European public assessment report (EPAR), and will be available in all official European Union languages after a decision on this change to the marketing authorisation has been granted by the European Commission.
https://www.retevmo.com/what-is-ret#testing-for-ret
EMA panel recommends extending indication for Lilly's cancer therapy
Apr. 22, 2022 12:32 PM ET Eli Lilly and Company (LLY)
By: Dania Nadeem, SA News Editor
- The European Union drug regulator's Committee for Medicinal Products for Human Use has recommended extending the indication for Eli Lilly's (NYSE:LLY) Retsevmo to treat lung cancer.
- https://seekingalpha.com/news/3825852-ema-panel-recommends-extending-indication-for-lillys-cancer-therapy
- https://seekingalpha.com/symbol/LLY
- https://www.retevmo.com/what-is-ret#testing-for-ret
- https://www.lilly.com/
EDIT-301: Transfusion-dependent beta thalassemia (TDT)
Editas Medicine Receives FDA Rare Pediatric Disease Designation For EDIT-301 For The Treatment Of Beta Thalassemia
April 26, 2022 at 9:00 AM EDTDownload PDF
CAMBRIDGE, Mass., April 26, 2022 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, today announced that the U.S. Food and Drug Administration (FDA) granted Rare Pediatric Disease designation to EDIT-301, an investigational, gene-edited medicine for the treatment of beta thalassemia. The FDA previously granted Rare Pediatric Disease designation to EDIT-301 for the treatment of sickle cell disease.
“Beta thalassemia is a devastating disease that leads to severe anemia, organ failure, and premature death. Receiving Rare Pediatric Disease designation for EDIT-301 for beta thalassemia highlights the dire need for new treatment options,” said James C. Mullen, Chairman, President, and Chief Executive Officer, Editas Medicine. “EDIT-301 is a potentially transformative medicine for patients living with beta thalassemia, and we look forward to dosing the first patient in our clinical trial this year.”
The FDA defines a rare pediatric disease as a serious or life-threatening disease in which the disease manifestations primarily affect individuals aged from birth to 18 years. Pediatric diseases recognized as “rare” affect fewer than 200,000 people in the United States.
Under the FDA’s Rare Pediatric Disease Designation and Voucher Programs, if Editas receives marketing approval for EDIT-301 for beta thalassemia, the Company may be eligible to receive a Priority Review Voucher (PRV) from the FDA that can be redeemed to receive priority review of a subsequent marketing application for a different product, or the PRV may be sold or transferred.
EDIT-301 is being investigated in a clinical study in patients with severe SCD (RUBY trial, NCT04853576). Editas expects to initiate a Phase 1/2 study of EDIT-301 in patients with transfusion-dependent beta thalassemia in 2022.
About EDIT-301
EDIT-301 is an experimental cell therapy medicine under investigation for the treatment of severe sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT). EDIT-301 consists of patient-derived CD34+ hematopoietic stem and progenitor cells edited at the gamma globin gene (HBG1 and HBG2) promoters, where naturally occurring fetal hemoglobin (HbF) inducing mutations reside, by a highly specific and efficient proprietary engineered AsCas12a nuclease. Red blood cells derived from EDIT-301 CD34+ cells demonstrate a sustained increase in fetal hemoglobin production, which has the potential to provide a one-time, durable treatment benefit for people living with severe sickle cell disease and transfusion-dependent beta thalassemia.
For the latest information and scientific presentations, please visit www.editasmedicine.com.
Editas gets FDA rare pediatric disease status for gene-edited drug EDIT-301 for beta thalassemia
Apr. 26, 2022 9:46 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) granted rare pediatric disease designation to Editas Medicine's (NASDAQ:EDIT) gene-edited medicine EDIT-301 to treat beta thalassemia, an inherited blood disorder.
- https://seekingalpha.com/news/3826797-editas-gets-fda-rare-pediatric-disease-status-for-gene-edited-drug-edit-301-for-beta-thalassemia
- https://seekingalpha.com/symbol/EDIT
- https://www.editasmedicine.com/gene-editing-pipeline/
VLA15 – Valneva’s Lyme disease vaccine candidate
Valneva and Pfizer Report Positive Phase 2 Pediatric Data for Lyme Disease Vaccine Candidate
April 26, 2022
- Strong immunogenicity profile observed in study participants aged 5-17 years one month after the primary vaccination series
- Safety profile observed in pediatric participants similar to previously reported data in adult participants
- Pediatric population to be included in planned Phase 3 trial – expected to start in Q3 2022, subject to regulatory approval
Saint-Herblain (France) and New York, April 26, 2022 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, and Pfizer Inc. (NYSE: PFE) today reported positive Phase 2 pediatric data for their Lyme disease vaccine candidate, VLA15. Based on these new results, Valneva and Pfizer plan to proceed with inclusion of pediatric participants in their planned Phase 3 trial. The trial will evaluate VLA15 in adults and pediatric subjects 5 years of age and above and is expected to be initiated in the third quarter of 2022, subject to regulatory approval.
The Phase 2 trial, VLA15-221, is the first clinical study with VLA15 which enrolled a pediatric population (5-17 years old). It compared the immunogenicity and safety of VLA15 after administration of two (at months 0 and 6) or three (at months 0, 2 and 6) primary series doses in groups aged 5-11, 12-17 and 18-65 years. In pediatric participants (5-17 years old) who received VLA15 in either the two-dose schedule (N=93) or three-dose schedule (N=97), VLA15 was found to be more immunogenic than in adults with both vaccination schedules tested. These data build on the strong immunogenicity profile already reported for adult participants (18-65 years old) in February 2022[1]. Like in adults, the immunogenicity and safety data support a three-dose primary vaccination schedule in pediatric participants in the Phase 3 study.
The safety and tolerability profile observed in the 5- to 17-year age group was similar to the previously reported profile in adult participants. No vaccine-related serious adverse events (SAEs) were observed.
Valneva and Pfizer plan to submit these data for publication and presentation at a future scientific congress.
Juan Carlos Jaramillo M.D., Chief Medical Officer of Valneva, said, “Lyme disease affects all age groups, but with their affinity for being active outdoors, the pediatric population is at the greatest risk of Lyme disease. These first pediatric results are therefore extremely important and support the inclusion of pediatric participants in our planned Phase 3 trial. In partnership with Pfizer, we are excited to further investigate our VLA15 vaccine candidate, which will hopefully help protect both adults and children against Lyme disease.”
Kathrin U. Jansen, Ph.D., Senior Vice President and Head of Vaccine Research & Development at Pfizer, said: “The medical need for vaccination against Lyme disease is steadily increasing as the geographic footprint of the disease widens. These positive pediatric data mark an important step forward in the ongoing development of VLA15, and we are excited to continue working with Valneva to potentially help protect both adults and children from Lyme disease.”
About VLA15
VLA15 is the only Lyme disease vaccine candidate currently in clinical development. This investigational multivalent protein subunit vaccine uses an established mechanism of action for a Lyme disease vaccine that targets the outer surface protein A (OspA) of Borrelia burgdorferi, the bacteria that cause Lyme disease. OspA is one of the most dominant surface proteins expressed by the bacteria when present in a tick. Blocking OspA inhibits the bacterium’s ability to leave the tick and infect humans. The vaccine covers the six most common OspA serotypes expressed by Borrelia burgdorferi sensu lato species that are prevalent in North America and Europe. VLA15 has demonstrated a strong immunogenicity and safety profile in pre-clinical and clinical studies so far. The program was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in July 20172. Valneva and Pfizer entered into a collaboration agreement in April 2020 to co-develop VLA153.
About Clinical Study VLA15-221
VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. It is the first clinical study with VLA15 which enrolled a pediatric population (5-17 years old).
585 healthy participants received VLA15 at two different immunization schedules (month 0-2-6 [N=190] or month 0-6 [N=187]) or three doses of placebo (month 0-2-6 [N=208]). Vaccine recipients received VLA15 at a dose of 180 µg, which was selected based on data generated in the two previous Phase 2 studies. The main safety and immunogenicity readout was performed one month after the primary vaccination series. A subset of participants will receive a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence.
VLA15 is tested as an alum-adjuvanted formulation and administered intramuscularly. The study is being conducted at U.S. sites located in areas where Lyme disease is endemic and has enrolled both volunteers with a cleared past infection with Borrelia burgdorferi as well as Borrelia burgdorferi-naïve volunteers.
About Valneva SE
Valneva is a specialty vaccine company focused on the development and commercialization of prophylactic vaccines for infectious diseases with significant unmet medical need. The Company takes a highly specialized and targeted approach to vaccine development and then applies its deep understanding of vaccine science to develop prophylactic vaccines addressing these diseases. Valneva has leveraged its expertise and capabilities both to successfully commercialize two vaccines and to rapidly advance a broad range of vaccine candidates into and through the clinic, including candidates against Lyme disease, the chikungunya virus and COVID-19.
In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Pfizer, Valneva Lyme disease vaccine shows response in kids over 5 in phase 2 trial
Apr. 26, 2022 5:57 AM ET
By: Ravikash, SA News Editor
Pfizer (NYSE:PFE) Valneva (NASDAQ:VALN) said they plan to include children above 5 years of age in a planned phase 3 trial of their Lyme disease vaccine VLA15 after positive pediatric data was reported from a phase 2 trial, which included children aged 5 years to 17 years, among others.
https://seekingalpha.com/symbol/VALN
https://seekingalpha.com/symbol/PFE
biotecMAX™ Feb/Mar/APR 2022 Insight
ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Enhertu granted Priority Review in the US for patients with previously treated HER2-mutant metastatic non-small cell lung cancer
PUBLISHED19 April 2022 19 April 2022 07:00 BST
Based on pivotal DESTINY-Lung01 results showing AstraZeneca and Daiichi Sankyo’s Enhertu demonstrated a 54.9% tumour response rate
If approved, Enhertu to provide patients with a much-needed targeted therapy option
AstraZeneca and Daiichi Sankyo have received notification of acceptance of the supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 (ERBB2) mutation and who have received a prior systemic therapy. The application has also been granted Priority Review.
Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the third quarter of 2022. The Priority Review follows Breakthrough Therapy Designation granted by the FDA for Enhertu in this cancer type in May 2020.
Lung cancer is the second most common form of cancer globally, with more than two million new cases diagnosed in 2020.2 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.3 There are currently no HER2-directed therapies approved specifically for the treatment of HER2-mutant NSCLC,4 which occurs in approximately 2-4% of patients with non-squamous NSCLC.4,5
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The DESTINY-Lung01 trial confirmed the HER2 mutation as an actionable biomarker in non-small cell lung cancer. If approved, Enhertu has the potential to become a new standard treatment in this patient population, offering a much-needed option for patients with HER2-mutant metastatic non-small cell lung cancer who currently have no targeted treatment options.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The results of DESTINY-Lung01 showed that Enhertu is the first HER2-directed therapy to demonstrate a strong and robust tumour response in more than half of patients with previously treated HER2-mutant metastatic non-small cell lung cancer. Seeking approval in the US for a third tumour type in three years further demonstrates the significant potential of Enhertu in treating multiple HER2-targetable cancers.”
The sBLA is based on data from the registrational DESTINY-Lung01 Phase II trial published in The New England Journal of Medicine, and is supported by the Phase I trial (DS8201-A-J101) published in Cancer Discovery.
Primary results from previously-treated patients with HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated a confirmed objective response rate (ORR) of 54.9% (95% confidence interval [CI]: 44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by independent central review (ICR). One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed.
A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for Enhertu was 9.3 months. The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.
The safety profile of the most common adverse events with Enhertu in DESTINY-Lung01 was consistent with previous clinical trials with no new safety concerns identified.
Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
DESTINY-Lung01
DESTINY-Lung01 is a global Phase II, open-label, two-cohort trial evaluating the safety and efficacy of Enhertu in patients with HER2-mutant (6.4mg/kg) or HER2-overexpressing (defined as IHC3+ or IHC2+) [6.4mg/kg and 5.4mg/kg] unresectable and/or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by ICR. Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled approximately 180 patients at multiple sites, including Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu gets FDA priority review in lung cancer subtype
Apr. 19, 2022 4:36 AM ET AstraZeneca PLC (AZN), DSNKYDSKYF