May 21, 2021
LYRICS: Can’t escape disappointment Can’t avoid the delay But I don’t have to make feeling down and defeated the place that I stay Gonna rise to the moment Gonna speak to the waves Gonna push back the doubt that keeps dragging me down when I can’t find the way Don’t need to see it (eyes on You) To believe it (for my breakthrough) Before You even move or make a way I will stand in faith (eyes on You) Walk by faith (for my breakthrough) Live by faith (before You move) I believe, I believe, I believe Stand in faith (eyes on You) See by faith (for my breakthrough) Receive by faith (before You move) I believe, I believe, I believe It’s a season for healing It’s a season for change To see miracles happen that no one can fathom as heaven invades It’s more than a feeling And it’s anchored in praise And when it’s the darkest it reaches the farthest and opens the way This is how blind men get their sight This is how dead men start to rise This is how small things multiply Nothing’s impossible Nothing’s impossible This is where oceans have to part This is where light cuts through the dark This is where I see who You are Nothing’s impossible Nothing’s impossible Stir my faith Stir my faith
#DannyGokey #StandInFaith #LyricVideo #Official Music video by Danny Gokey performing Stand In Faith (Lyric Video). Sparrow Records; © 2021 Danny Gokey, under exclusive license to Capitol Christian Music Group, Inc.
SAN DIEGO, Jan. 21, 2022 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, today announced positive results from a Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib at the 600mg BID dose in patients with pretreated pancreatic ductal adenocarcinoma and other gastrointestinal (GI) tumors harboring a KRASG12C mutation, including cancers of the biliary tract, appendix, small bowel, gastro-esophageal junction, and esophagus. Results showed that adagrasib demonstrated significant clinical activity and broad disease control. The findings (Abstract # 519) will be presented today at 10:00 a.m. ET during a rapid abstract session at the 2022 American Society for Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.
Dr. Tanios S. Bekaii-Saab, an investigator of the KRYSTAL-1 study, commented, "Gastrointestinal cancers are some of the most common cancers and continue to be associated with poor survival outcomes despite recent advances, especially in patients with GI tumors harboring a KRASG12C mutation. New clinical data presented at ASCO GI show that adagrasib, an inhibitor of KRASG12C, demonstrated promising clinical activity in patients with pancreatic cancer and other GI tumors. These findings build on the previously reported positive adagrasib clinical data in colorectal and pancreatic cancers, and are highly encouraging, warranting further investigation of adagrasib in this setting."
Summary of Clinical Results
"We believe adagrasib has a differentiated molecular profile, and the data presented at ASCO GI further support its potential best-in-class profile," said Charles M. Baum, M.D., Ph.D., founder, president and head of research and development, Mirati Therapeutics, Inc. "The results demonstrated positive clinical activity in patients with KRASG12C-mutated GI cancers treated with single agent adagrasib, particularly in those with pancreatic cancer where options are limited. We continue to aggressively evaluate adagrasib as a single agent and in combination with other cancer medicines in a broad development plan to help more people living with cancer."
About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.
For more information about Mirati Therapeutics, visit us at Mirati.com or follow us on Twitter and LinkedIn.
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SOURCE Mirati Therapeutics, Inc.
Jan. 21, 2022 11:22 AM ET
By: Ravikash, SA News Editor
Jan 21, 2022
– Vutrisiran Met All 18 Month Secondary Endpoints, Including Statistically Significant Improvements in Neuropathy Impairment, Quality of Life (QoL), Gait Speed, Nutritional Status and Overall Disability, Relative to External Placebo –
– Vutrisiran Continued to Demonstrate Halting or Reversal of Polyneuropathy, with Improvements in Neuropathy Impairment and QoL Relative to Baseline –
– Exploratory Cardiac Data, Including Reduced Technetium Uptake Relative to Baseline in Majority of Assessable Patients, Continue to Support Potential for Vutrisiran to Reduce Cardiac Amyloid Burden and Improve Cardiac Manifestations of Disease –
– In Addition, Vutrisiran Continued to Demonstrate Encouraging Safety and Tolerability Profile –
– Alnylam to Host Conference Call Today at 8:30 am ET –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 21, 2022-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, met all secondary endpoints measured at 18 months in patients with hATTR amyloidosis with polyneuropathy, including statistically significant improvements in neuropathy impairment, quality of life (QoL), gait speed, nutritional status and overall disability, relative to placebo, and non-inferiority of serum TTR reduction relative to the within-study patisiran arm. The results were presented today in an oral session at the Société Francophone du Nerf Périphérique (SFNP) Annual Meeting.
In HELIOS-A, patients treated with vutrisiran also showed improvement in exploratory cardiac endpoints including NT-proBNP and echocardiographic parameters relative to placebo, as well as technetium uptake, relative to baseline, in a planned cohort of patients. Vutrisiran also continued to demonstrate an encouraging safety and tolerability profile consistent with the previously reported Month 9 results. Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at 9 months and study results were presented at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.
“These HELIOS-A results show that the improvement in neuropathy impairment and quality of life observed with vutrisiran at 9 months is maintained through Month 18, with the treatment effect increasing over time and an encouraging safety profile. Further, we are encouraged by the exploratory cardiac endpoint results, particularly new data indicating that 18 months of vutrisiran treatment resulted in reduced technetium uptake in the heart compared to baseline in the majority of patients who were in a planned cohort, suggesting the potential for amyloid regression. We look forward to seeing data from the APOLLO-B and HELIOS-B studies, which are investigating the potential of patisiran and vutrisiran, respectively, to treat the cardiac manifestations of disease in patients with ATTR amyloidosis with cardiomyopathy,” said Rena N. Denoncourt, Vice President, TTR Franchise Lead. “Vutrisiran is currently under review by multiple regulatory authorities around the world, bringing us a step closer to potentially making this low-dose, once-quarterly, subcutaneously administered treatment option available for patients living with the polyneuropathy of hATTR amyloidosis, and furthering our efforts to build an industry-leading franchise of medicines for the treatment of ATTR amyloidosis.”
HELIOS-A 18-Month Study Results
At 18 months, vutrisiran met all secondary endpoints in HELIOS-A, demonstrating statistically significant improvement in clinical endpoints compared to placebo and non-inferiority in serum TTR reduction compared to the within-study patisiran arm, specifically:
Vutrisiran demonstrated an encouraging safety profile in HELIOS-A at 18 months. There were three study discontinuations (2.5 percent) due to adverse events in the vutrisiran arm by Month 18, one due to a non-fatal event of heart failure and two due to deaths, neither of which was considered related to the study drug. During the 18-month treatment period there were two serious adverse events (SAEs) deemed related to vutrisiran by the study investigator, consisting of dyslipidemia and urinary tract infection. The two deaths and the two related SAEs were previously reported at Month 9.
Treatment emergent adverse events (AEs) occurring in 10 percent or more patients included fall, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia and dizziness; with the exception of pain in extremity and arthralgia, each of these events occurred at a similar or lower rate as compared with external placebo. Injection site reactions (ISRs) were reported in five patients (4.1 percent) and were all mild and transient. There were no clinically significant changes in liver function tests (LFTs).
To view the data presented by Alnylam at SFNP, please visit, Capella
“The 18-month results of the HELIOS-A Phase 3 study build on the results observed at 9 months and continue to underscore the potential of vutrisiran as an attractive new treatment option that can be administered subcutaneously four times a year,” said David Adams, M.D., Ph.D., Department of Neurology, Bicetre hospital, Greater Paris University Hospitals, AP-HP, University Paris Saclay and Principal Investigator for the HELIOS-A trial. “The data presented today are exciting, demonstrating additional progress from ongoing research focused on meeting the needs of this diverse group of patients living with a progressive, life-threatening, multi-system disease, with a potential new option that may help simplify their treatment.”
Vutrisiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hATTR and wild-type ATTR (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, potentially blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. Quarterly, and potentially biannual, administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability that may allow for infrequent subcutaneous injections. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency, or any other health authority.
About HELIOS-A Phase 3 Study
HELIOS-A (NCT03759379) is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran. The study enrolled 164 patients with hATTR amyloidosis with polyneuropathy at 57 sites in 22 countries. Patients were randomized 3:1 to receive either 25mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (as a reference comparator) for 18 months. The efficacy results of vutrisiran in HELIOS-A are compared to the placebo group from the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in a patient population similar to that studied in HELIOS-A. The primary endpoint is the change from baseline in mNIS+7 at 9 months. Secondary endpoints at 9 months are the change from baseline in the Norfolk QoL-DN score and the timed 10-MWT. Changes from baseline in NT-proBNP were evaluated as an exploratory endpoint at 9 months. Additional secondary endpoints at 18 months were evaluated in the HELIOS-A study, including change from baseline in mNIS+7, Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI), Rasch-built Overall Disability Scale (R-ODS), and serum transthyretin (TTR) levels. Additional exploratory cardiac endpoint data at the 18-month time point include NT-proBNP, echocardiographic measures and cardiac amyloid assessments with technetium scintigraphy imaging. Following the 18-month treatment period, all patients are eligible to receive vutrisiran for an additional 18 months as part of the randomized treatment extension where they will receive either 25mg vutrisiran once quarterly or 50mg vutrisiran once every six months.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220121005075/en/
Source: Alnylam Pharmaceuticals, Inc.
Jan. 21, 2022 8:26 AM ET
By: Dulan Lokuwithana, SA News Editor
January 18, 2022PDF Version- DKN-01 plus tislelizumab demonstrated encouraging clinical activity in both first- and second-line advanced gastric or gastroesophageal junction cancer patients
- 10.7 months PFS in overall first-line population; higher 11.9 months PFS in DKK1-high patients
- Company to host conference call on Friday, January 21, 2022 at 1:00 p.m. ET
CAMBRIDGE, Mass., Jan. 18, 2022 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced the Company will be presenting updated data from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap's anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene's anti-PD-1 antibody, in patients with gastric or gastroesophageal junction cancer (G/GEJ), at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium being held on January 20-22, 2022.
The Company will host a conference call with Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital on Friday, January 21, 2022 to discuss results from the study.
The latest results from Part A of the DisTinGuish study will be presented, representing first-line advanced G/GEJ patients treated with DKN-01 in combination with tislelizumab and chemotherapy. New data demonstrate compelling efficacy from this combination regimen, driven by enhanced clinical responses and survival benefit associated with high tumoral DKK1 expression that is independent of PD-L1 expression. Also to be presented are initial findings from the still-enrolling Part B of the clinical trial, studying DKN-01 and tislelizumab in second-line advanced G/GEJ patients with high tumoral DKK1 expression, showing the treatment is well tolerated with encouraging objective responses observed.
"The combination of DKN-01 with tislelizumab continues to demonstrate encouraging results in patients with gastric and gastroesophageal junction cancer, especially those in the DKK1-high subpopulation," said Samuel Klempner, MD, Associate Professor at Harvard Medical School who leads the gastric and esophageal cancer program at Massachusetts General Hospital Cancer Center and is a principal investigator on the DisTinGuish study. "The updated front-line results are encouraging in a difficult to treat cohort of primarily PD-L1 low patients, who are less likely to benefit from anti-PD-1 therapy. Together with encouraging initial findings from Part B, where DKN-01 and tislelizumab are used as a chemo-free second-line treatment of DKK1 high-expressing tumors, these results continue to support the therapeutic potential of DKN-01 and warrant exploration in a randomized clinical trial in first-line gastric and gastroesophageal junction patients."
About the DisTinGuish Study
The DisTinGuish study (NCT04363801) is a Phase 2a study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in two parts in the United States and the Republic of Korea. Enrollment of Part A has been completed with 25 first-line HER2- G/GEJ cancer patients whose tumors express either high levels of DKK1 (DKK1-high) or low levels of DKK1 (DKK1-low). Part B of the study has enrolled 30 patients with second-line DKK1-high G/GEJ cancer and will continue to enroll up to 48 patients. Leap is conducting this combination study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.
For more information about Leap Therapeutics, visit http://www.leaptx.com or view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/.
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SOURCE Leap Therapeutics, Inc.
Jan. 19, 2022 8:35 AM ET
By: Dulan Lokuwithana, SA News Editor
-- SEA-CD40 with Chemotherapy and an Anti-PD-1 Showed Evidence of Immune Activation, Preliminary Antitumor Activity, and an Acceptable Safety Profile --
BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq:SGEN) today announced data from a phase 1 clinical trial combining SEA-CD40 with chemotherapy and an anti-PD-1 in patients with metastatic PDAC at the ASCO GI annual meeting taking place in San Francisco, January 20 – 22, 2022. SEA-CD40 is a novel, investigational, nonfucosylated monoclonal receptor-agonistic antibody directed to CD40, which is expressed on antigen-presenting cells. In preclinical models, the combination of SEA-CD40 and chemotherapy resulted in antitumor activity which is further enhanced with anti-PD-1 treatment.
In the ongoing phase 1 trial, SEA-CD40 was combined with chemotherapy [gemcitabine and nab-paclitaxel (GnP)], and an anti-PD-1 (pembrolizumab), in 61 patients with untreated metastatic PDAC. Of these, 40 patients received 10 mcg/kg and 21 patients received 30 mcg/kg of SEA-CD40. Key endpoints include confirmed objective response rate (cORR) per RECIST v1.1 by investigator, progression-free survival (PFS) and overall survival (OS).
Activity of SEA-CD40 in combination with GnP and pembrolizumab was observed in both doses of SEA-CD40 tested. The overall (N = 61) cORR was 44 percent, median PFS was 7.4 months (95 percent CI: 5.6-9.0), and median OS was 15.0 months (95 percent CI: 7.8-19.9).
Follow-up for efficacy is ongoing.
The regimen demonstrated a manageable and tolerable safety profile. Overall, ≥ grade 3 treatment-emergent adverse events (TEAEs) were fatigue, nausea, neutropenia, infusion-related reaction, chills, diarrhea, and pyrexia.
This combination also showed evidence of immune activation consistent with the SEA-CD40 mechanism of action.
“Preliminary activity is encouraging based on historical chemotherapy outcomes. Further survival follow up is required to inform our next steps in pancreatic cancer,” said Roger Dansey, M.D., Chief Medical Officer at Seagen. “We are continuing to advance the ongoing phase 2 trial of SEA-CD40 in melanoma and in non-small cell lung cancer.”
View source version on businesswire.com: https://www.businesswire.com/news/home/20220118006157/en/
Source: Seagen Inc.
Jan. 18, 2022 5:41 PM ET
Trial Reaches Milestone of Over 1000 Patients Screened
Addition of New Interventions – Biohaven Pharmaceuticals’ Troriluzole and Vigeo Therapeutics’ VT1021
Planned Expansion of Trial to Include Sites in Europe and China
January 18, 2022 04:15 PM Eastern Standard Time
LOS ANGELES--(BUSINESS WIRE)--Global Coalition for Adaptive Research (GCAR) today announced an update on the progress of GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment - NCT03970447). GBM AGILE is a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM) – the deadliest form of brain cancer.
GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE can be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the FDA and other health authorities.
Biohaven’s troriluzole is a novel, orally administered small molecule that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Troriluzole is thought to restore glutamate homeostasis by enhancing glutamate cycling, decreasing presynaptic glutamate release, and augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing excess glutamate from the synapse. Troriluzole was selected for inclusion in GBM AGILE, based on compelling evidence showing deregulation of glutamate in glioblastoma. The therapeutic potential of troriluzole in glioblastoma and other oncology indications is supported by several recent clinical and translational research studies conducted with troriluzole and its active moiety.
About Global Coalition for Adaptive Research (GCAR)
The Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) nonprofit organization uniting physicians, clinical researchers, advocacy and philanthropic organizations, biopharma, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases by serving as sponsor of innovative and complex trials including master protocols and platform trials. GCAR is the sponsor of GBM AGILE, an adaptive platform trial for patients with GBM – the most common and deadliest of malignant primary brain tumors. Key strategic partners for the GBM AGILE trial effort include the National Brain Tumor Society, National Foundation for Cancer Research, and Asian Fund for Cancer Research, three nonprofit organizations that are working together to provide philanthropic support as well as assistance in communicating with patients and families and inviting all others to join in supporting this innovating approach to brain tumor treatment development.
Jan. 18, 2022 4:46 PM ET
By: Dulan Lokuwithana, SA News Editor
January 10, 2022
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced it has entered into two clinical trial collaboration and supply agreements with Merck (known as MSD outside of the United States and Canada) to evaluate the combination of Gilead’s Trop-2 targeting antibody-drug conjugate (ADC) Trodelvy® (sacituzumab govitecan-hziy) and Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in first-line metastatic non-small cell lung cancer (NSCLC). As part of the collaboration, Merck will sponsor a global Phase 3 clinical trial of Trodelvy in combination with KEYTRUDA as a first-line treatment for patients with metastatic NSCLC. Additionally, the companies recently established an agreement whereby Gilead will sponsor a Phase 2 signal-seeking study evaluating combinations that include pembrolizumab in first-line NSCLC.
“We’re excited to broaden our clinical collaborations with Merck to investigate Trodelvy in combination with KEYTRUDA in another cancer where there is tremendous need for novel combinations to help improve patient outcomes,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “This partnership builds on our ambition of providing alternatives to traditional chemotherapy with Trodelvy containing regimens across some of the most difficult-to-treat cancers.”
NSCLC is the most common type of lung cancer and accounts for up to 85% of cases. It is an aggressive disease with poor prognosis. Although there has been significant progress in recent years in the treatment of the disease, there is a still a major unmet need for patients with only 25% of patients surviving beyond five years.
Trodelvy is an antibody-drug conjugate that specifically targets Trop-2 expressing cells to enable local delivery of a cytotoxic payload that selectively kills the targeted cells. The combination of Trodelvy with an immune-stimulating agent such as KEYTRUDA could provide a new treatment option for a broader set of patients with first-line metastatic NSCLC.
The use of Trodelvy for the treatment of NSCLC is investigational, and the safety and efficacy for this use have not been established or approved by any regulatory agency globally. In the United States, Trodelvy is approved for the treatment of second-line metastatic triple-negative breast cancer (TNBC),and has additionally been approved under the accelerated approval pathway for the treatment of metastatic urothelial cancer (UC) in adults who have received certain prior therapies. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information for Trodelvy.
Everest Medicines will also participate in the global Phase 3 study in Asia through its existing collaboration agreement with Gilead.
These agreements follow a collaboration, established in October 2021, to investigate Trodelvy in combination with KEYTRUDA as first-line treatment for people with locally advanced or metastatic triple-negative breast cancer (TNBC).
The use of Trodelvy for the treatment of NSCLC and the use of Trodelvy in combination with KEYTRUDA for any use is investigational, and the safety and efficacy for these uses have not been established or approved by regulatory agency globally.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer (including both NSCLC and small-cell lung cancer (SCLC)) is the second most common cancer in both men and women and is the leading cause of cancer death, making up approximately 25% of all cancer deaths. NSCLC is the most common type of lung cancer and accounts for up to 85% of cases. It is an aggressive disease with poor prognosis, and the relative five-year survival rate is 25%.
Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Trodelvy is approved for adults with second-line metastatic TNBC in the United States, the European Union, Australia, Canada, Great Britain and Switzerland. Trodelvy is also under multiple regulatory reviews worldwide, including in Singapore and China through our partner Everest Medicines. Trodelvy continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.
U.S. Indication for Trodelvy
In the United States, Trodelvy is indicated for the treatment of:
Please see full Prescribing Information , including BOXED WARNING.
U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at www.gilead.com.
Trodelvy, Gilead and the Gilead logo are 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 (@GileadSciences) 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/20220107005485/en/
Source: Gilead Sciences, Inc.
Jan. 10, 2022 8:30 AM ET
RESEARCH TRIANGLE PARK, N.C., Jan. 07, 2022 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced the enrollment of the first patient in the REDEEM-1 pivotal trial with its oral Factor D inhibitor, BCX9930, in patients with paroxysmal nocturnal hemoglobinuria (PNH).
REDEEM-1 is a randomized, open-label, active comparator-controlled comparison of the efficacy and safety of BCX9930 (500 mg bid) monotherapy in approximately 81 PNH patients with an inadequate response to a C5 inhibitor. In part 1 of this trial, patients who have not had an adequate response to a C5 inhibitor will be randomized 2:1 to discontinue their C5 inhibitor and receive BCX9930 as monotherapy or to continue receiving their C5 inhibitor for 24 weeks. All patients will receive BCX9930 in part 2 (weeks 25-52) to assess the long-term safety, tolerability and effectiveness of BCX9930. Patients who are randomized to C5 inhibitor therapy in part 1 will discontinue that therapy at the week 24 visit and start BCX9930 for part 2. The primary endpoint of REDEEM-1 is change from baseline in hemoglobin, as assessed at weeks 12 to 24.
“On the heels of recently beginning enrollment in our REDEEM-2 pivotal trial, today’s announcement marks another important milestone as we advance BCX9930 closer to registration for patients living with PNH,” said Dr. William Sheridan, chief medical officer of BioCryst. “Given the unmet need patients have related to the current standard of care, we aim to demonstrate in the REDEEM-1 pivotal trial the potential of BCX9930 as an oral monotherapy that could represent significant improvement for patients compared to their experiences with C5 inhibitor therapies.”
In a dose-ranging trial of BCX9930 in C5 inadequate response patients, the company previously reported that BCX9930 (at doses of 400 mg or 500 mg bid) increased hemoglobin from baseline by a mean of 2.7 g/dL through weeks 12 to 24 with 80 percent of patients being transfusion-free over the same period. BCX9930 was safe and generally well-tolerated in the trial.
BioCryst recently announced it had begun enrolling patients in the REDEEM-2 pivotal trial, a randomized, placebo-controlled trial to evaluate the efficacy and safety of BCX9930 (500 mg bid) as monotherapy versus placebo in approximately 57 PNH patients not currently receiving complement inhibitor therapy. Additionally, the company is initiating a proof-of-concept trial of BCX9930 in renal complement-mediated diseases including C3 glomerulopathy (C3G), IgA nephropathy (IgAN) and primary membranous nephropathy (PMN).
The U.S. Food and Drug Administration has granted both Fast Track status and Orphan Drug Designation to BCX9930 for PNH. For more information about REDEEM-1, visit ClinicalTrials.gov and search NCT number NCT05116774.
For more information, please visit the company’s website at www.biocryst.com.
Dusquetide Demonstrates Positive Anti-tumor Efficacy in Multiple Nonclinical Animal StudiesComplementary treatment with chemotherapy, radiation and targeted therapy supports development as potential anti-cancer agent
PRINCETON, N.J., Jan. 4, 2022 /PRNewswire/ -- Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that dusquetide is effective at reducing tumor size in nonclinical xenograft models. Recent studies, recapitulating results from previously published studies, have confirmed the efficacy of dusquetide as a stand-alone and combination anti-tumor therapy, with radiation, chemotherapy and targeted therapy, in the context of the MCF-7 breast cancer cell line. Dusquetide previously demonstrated benefits in reducing the duration of severe oral mucositis (SOM) in a Phase 2 clinical trial and reduction in SOM rates in the per protocol population in a Phase 3 study. In addition to the reduction of severe oral mucositis, an acceleration in the clearance of tumor response and an increase in overall survival were also observed in the Phase 2 clinical study as an ancillary benefit to treating oral mucositis in patients receiving chemo-radiation for their head and neck cancer (HNC).
Based on the biological proof of principle shown both nonclinically and clinically with dusquetide, a novel synthetic peptide that modulates the body's innate immune system, Soligenix continues to explore product opportunities, both in the reduction of oral mucositis in HNC and as a potential anti-cancer treatment. Dusquetide binds to p62 or SQSTM-1, a scaffold protein implicated in a number of intracellular signaling networks implicated in tumor cell survival, including autophagy. The role of p62 is best characterized in multiple myeloma and breast cancer. All variants of breast cancer, including metastatic breast cancer, estrogen receptor positive (ER+), human epidermal growth factor receptor 2 high expressing (HER2+) and triple negative expressing cell lines, have demonstrated a significant role for p62 in tumorigenesis.
The MCF-7 cell line tested in the xenograft studies with dusquetide is both ER+ and responsive to anti-HER2 treatment. Treatment with dusquetide was effective not only as a stand-alone treatment (p<0.01 for tumor size), but also in conjunction with radiation (p<0.05 vs radiation only for survival), chemotherapy (paclitaxel) and targeted treatment (trastuzumab; p<0.001 vs. placebo only for tumor size), reducing tumor size and enhancing overall survival. Other tumor types also have been shown to be dependent on p62 expression, including multiple myeloma, liver cancer (hepatocellular carcinoma), lung cancer (non-small cell lung cancer, EGFR-TKI-resistant lung cancer), intestinal cancer (small intestinal adenocarcinoma and gastric cancer), and colorectal cancer and ovarian cancer (multi-drug resistant).
"Soligenix continues to pursue potential product opportunities with our new chemical entity dusquetide, including in oncology," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "With the supportive data from the Phase 2 and 3 oral mucositis trials, and the nonclinical anti-tumor efficacy demonstrated, we continue to pursue potential partnership for this novel molecule."
Dusquetide (the active ingredient in SGX942) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis. Potential anti-tumor activity has been demonstrated in in vitro and in vivo xenograft studies.
SGX942 has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in an exploratory Phase 2 clinical study (Study IDR-OM-01) in 111 patients with oral mucositis due to CRT for HNC, including potential long term ancillary benefits. The Phase 3 multinational, placebo-controlled, randomized study evaluated the impact of dusquetide on the duration of SOM in 268 subjects with squamous cell carcinoma of the oral cavity and oropharynx, scheduled to receive a minimum total cumulative radiation dose of 55 Gy with concomitant cisplatin chemotherapy. A clinically meaningful reduction in the duration of SOM was observed in the ITT population and a clinically and statistically significant reduction was observed in the per protocol population.
SGX942 has received Fast Track Designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, as well as Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT. In addition, products containing the same active ingredient, dusquetide, have been granted Fast Track Designation as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis and Orphan Drug Designations in the treatment of MAS and the treatment of acute radiation syndrome.
Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies. The Phase 2 study was supported with a Phase I SBIR grant (#R43DE024032) award, with the Phase 3 study being supported by a Phase II SBIR grant (#R44DE024032) award.
In addition, a high level review of the IDR technology platform is available here.
Jan. 04, 2022 8:06 AM ET
By: Dulan Lokuwithana, SA News Editor
Vaccinex Reports Phase Ib KEYNOTE B84 Combination Study of Keytruda® and Pepinemab in Patients with Advanced, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Passes Planned Interim Safety Analysis
Phase 1b segment evaluated safety and tolerability of the combination
Paves the way to expand and accelerate enrollment in the Phase 2 segment of the study
ROCHESTER, N.Y., Jan. 04, 2022 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX, Vaccinex, the Company), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, today reported positive interim safety data in the Phase Ib “safety run-in” segment of the KEYNOTE B84 combination study of Keytruda® (Merck, NYSE: MRK, known as MSD outside of the United States and Canada) and pepinemab (Vaccinex) in patients with advanced, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The Phase 2 segment of the study is now expected to begin enrollment and is expected to accelerate patient accrual.
The Phase Ib “safety run-in” segment of the trial (NCT04815720) was intended to evaluate the safety and tolerability of pepinemab (20 mg/kg) in combination with Keytruda (Merck’s anti-PD-1 therapy, pembrolizumab, 200 mg Q3W/every three weeks) to determine a recommended Phase 2 dose (RP2D) for the dose expansion phase of the study enrolling patients with R/M HNSCC. The interim safety analysis was completed by the Data Safety Monitoring Board and signals initiation of the Phase 2 expansion segment.
“We are very pleased that the interim KEYNOTE B84 safety data indicated that the combination of pepinemab and Keytruda appears to be well tolerated,” stated Maurice Zauderer, Ph.D., President and Chief Executive Officer. “Vaccinex hopes that the combination of pepinemab and an anti-PD-1 therapy for the treatment of advanced R/M HSNCC may result in improved patient benefits. There is strong rationale for development in HNSCC because these tumors express very high levels of SEMA4D and we believe that preclinical data indicated that this contributes to disease pathology. We look forward to progressing with the recruitment of the Phase 2 segment of the trial.”
About the KEYNOTE B84 Study:
The KEYNOTE B84 combination study of Keytruda® (Merck’s anti-PD-1 therapy, pembrolizumab) and pepinemab (Vaccinex’s monoclonal antibody inhibitor of SEMA4D) is being conducted for first line treatment of patients with advanced, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study has two segments:
Secondary objectives of the study are to evaluate Progression-Free Survival (PFS) by RECIST 1.1, Overall Survival (OS), and Duration of Response (DOR).
The study is also expected to evaluate a number of exploratory measures including the pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of the combination and a number of biomarkers and genomic tumor signatures.
Additional information about the study is available at: the KEYNOTE B84 clinicaltrials.gov link. Vaccinex anticipates interim results for the primary efficacy endpoint, ORR, in the second half of 2022.
Vaccinex will sponsor the study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc.
Vaccinex has global commercial and development rights to pepinemab.
Keytruda® is a trademark of Merck.
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates chronic inflammation in the tumor microenvironment. Preclinical/clinical data show that pepinemab promotes infiltration/activation of dendritic cells/ CD8+ T-cells and reverses immunosuppression within the tumor.
Results of a Phase 1b/2 study to evaluate the combination of pepinemab with checkpoint inhibitor, BAVENCIO®, (with Merck KGaA) were presented by Dr. Shafique, MD, Assistant Professor Thoracic Oncology, Moffitt Cancer Center, in an oral poster and discussion section at ASCO 2020 and were highlighted in the July 2021 publication of Clinical Cancer Research. Vaccinex reported that results of the Phase 1b/2 CLASSICAL-Lung trial showed a 25-33% Overall Response Rate (ORR) for patients with difficult to treat PD-L1 low/negative tumors treated with the combination, while reported ORR for similar patients treated with anti-PD-L1 monotherapy is ~10-15%. The study report also indicated that pepinemab did not increase immune-related toxicities of BAVENCIO but increased penetration of cytotoxic T cells. The publication is available electronically at: Clinical Cancer Research.
Jan. 04, 2022 9:18 AM ET
By: Mamta Mayani, SA News Editor
Suzhou, China, January, 3, 2022 - CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today announced that the investigational new drug (IND) application of CS5001, a potential global best-in-class antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1) has received a STUDY MAY PROCEED (SMP) letter from the U.S. Food and Drug Administration (FDA). CS5001 will commence in the clinic as one of the three most advanced ROR1 ADCs globally, marking another important milestone for CStone’s Pipeline 2.0 strategy.
ROR1 is an oncofetal protein with low or no expression in adult tissues but high expression in a variety of cancers including various forms of leukemia and non-Hodgkin lymphoma, breast, lung, and ovarian cancers, making it an ideal ADC target. CS5001 is an ADC targeting ROR1 with multiple differentiated features including proprietary site-specific conjugation, tumor-selective cleavable linker and pro-drug technology. Results from pre-clinical studies showed that CS5001 exhibited potent and selective cytotoxicity to a variety of ROR1-expressing cancer cell lines and demonstrated remarkable in vivo antitumor activity in both hematological and solid tumor xenograft models.
Dr. Archie Tse, Chief Scientific Officer of CStone, said, “We are glad that the IND application of CS5001 received the SMP letter from the U.S. FDA in 2021. The preclinical pharmacology data were encouraging and demonstrated CS5001’s therapeutic potential in multiple hematological and solid malignancies. There are only three ROR1 ADCs including CS5001 in clinical development. The upcoming first-in-human Phase I study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS5001 in advanced B cell lymphomas and solid tumors. We will make every effort to advance this clinical trial of CS5001, meanwhile we have already submitted the CTN application in Australia and plan to submit the IND application in China soon.”
About CS5001（ROR1 ADC）
In October 2020, CStone signed a licensing agreement with LegoChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to lead development and commercialization of CS5001 outside the Republic of Korea.
CS5001 is now a clinical-stage antibody-drug conjugate (ADC) targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has uniquely designed and LCB’s proprietary tumor-cleavable linker and pyrrolobenzodiazepine (PBD) prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps addressing the toxicity problem associated with traditional PBD payloads, leading to a better safety profile. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of 2 which enables homogeneous production and large-scale manufacturing.
For more information about CStone, please visit: www.cstonepharma.com.
Janssen Submits Biologics License Application to U.S. FDA Seeking Approval of Teclistamab for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma
RARITAN, N.J., December 29, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of teclistamab for the treatment of patients with relapsed or refractory (R/R) multiple myeloma. Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3.
“Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “We look forward to working with the FDA in their review of our teclistamab submission.”
The BLA submission for teclistamab is supported by data from MajesTEC-1 (NCT04557098, NCT03145181), an open-label, multicenter clinical trial evaluating the safety and efficacy of teclistamab in adults with R/R multiple myeloma. In the study, investigators assessed efficacy outcomes, including overall response rate, very good partial response and complete response using International Myeloma Working Group (IMWG) criteria, as well as the safety profile of teclistamab. Updated MajesTEC-1 data were recently presented at the American Society of Hematology annual meeting.
“The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “Today’s submission is another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health.”
Multiple myeloma is an incurable blood cancer that affects white blood cells called plasma cells, which are found in the bone marrow and normally make antibodies which fight infection., When these plasma cells become malignant and develop into multiple myeloma, these myeloma cells proliferate and replace normal cells in the bone marrow. In 2021, it is estimated that nearly 35,000 people will be diagnosed and more than 12,000 will die from this disease in the U.S. While some patients with multiple myeloma initially have no symptoms, many patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.
Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor. BCMA is expressed at high levels on multiple myeloma cells.,,,, Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.8
Teclistamab is currently being evaluated in several monotherapy and combination studies. In 2020, the European Commission and the U.S. FDA each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimize drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need. The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Dec. 29, 2021 8:29 AM ET
By: Dulan Lokuwithana, SA News Editor
SHANGHAI, China, and GAITHERSBURG, MD, December 27, 2021 - I-Mab (the “Company”) (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has approved I-Mab’s IND submission for the initiation of a phase 2 trial in China for enoblituzumab (also known as TJ271) in combination with pembrolizumab (Keytruda®) in patients with solid tumors, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and other selected cancers. I-Mab has acquired exclusive rights to develop and commercialize enoblituzumab in Greater China from MacroGenics (Nasdaq: MGNX).
Enoblituzumab is a highly differentiated humanized monoclonal antibody directed against the immune regulator B7-H3, which plays a key role in regulating immune response against cancers and is widely expressed in multiple cancers. The presence of B7-H3 in tumors is associated with the poor efficacy of neoadjuvant therapies. Enoblituzumab enhances the antibody-dependent killing of cancer cells and has demonstrated strong anti-tumor activity in preclinical studies. Additional preclinical data generated by I-Mab and preliminary clinical evidence from MacroGenics support increased efficacy for the combination of enoblituzumab and a PD-1 antibody against cancers.
The phase 2 clinical trial in China will evaluate the efficacy of the combination of enoblituzumab and pembrolizumab. The trial is designed as a "basket" clinical trial in patients with NSCLC, UC, and other selected cancer types based on previous studies conducted by MacroGenics. These previous studies have indicated that combination therapy resulted in anti-tumor activity in recurrent or metastatic NSCLC and squamous cell carcinoma of the head and neck (SCCHN).
"The initiation of the phase 2 clinical trial will accelerate the clinical development of enoblituzumab in China," said Dr. Andrew Zhu, President of I-Mab. "Enoblituzumab has become a key player against various advanced cancers and one of the Company’s core clinical assets. We are excited about the initiation of this clinical study and expect to bring this valuable compound to cancer patients with critical unmet medical needs."
Currently, MacroGenics is conducting a phase 2 study of enoblituzumab in combination with retifanlimab (PD-1 antibody) or tebotelimab (PD-1 & LAG-3 bispecific DART® molecule) for first-line treatment of patients with recurrent or metastatic SCCHN.
Enoblituzumab is an investigational Fc-optimized monoclonal antibody that targets B7-H3, a member of the B7 family of immune regulator proteins. B7-H3 is widely expressed by many different tumor types and may play a key role in regulating the immune response to various types of cancer. Enoblituzumab has been or is currently being evaluated in clinical trials as a monotherapy or in combination with anti-PD-1-based therapies in patients with B7-H3-expressing cancers. I-Mab acquired the development and commercial rights from MacroGenics for Greater China.
Patritumab Deruxtecan Granted U.S. FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer • First Breakthrough Therapy Designation for patritumab deruxtecan based on results of phase 1 trial • Seventh Breakthrough Therapy Designation granted by FDA across Daiichi Sankyo’s oncology portfolio Tokyo, Munich and Basking Ridge, NJ – (December 23, 2021) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to patritumab deruxtecan (HER3-DXd), a potential first-in-class HER3 directed antibody drug conjugate (ADC), for the treatment of patients with metastatic or locally advanced EGFR-mutated non-small cell lung cancer (NSCLC) with disease progression on or after treatment with a third-generation tyrosine kinase inhibitor (TKI) and platinum-based therapies. Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide, with 80% to 85% classified as NSCLC. 1,2,3 While the efficacy of targeted therapy with EGFR TKIs is wellestablished in the treatment of advanced EGFR-mutated NSCLC, which comprises approximately 30% of patients, the development of a broad range of resistance mechanisms commonly leads to disease progression. 4,5,6 After failure of an EGFR TKI, platinum-based chemotherapy haslimited efficacy with progression-free survival (PFS) of approximately 4.4 to 6.4 months. 7 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have PFS of 2.8 to 3.2 months. 8 The U.S. FDA’s 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. The FDA granted the BTD based on data from the dose escalation portion and two expansion cohorts of a three-cohort phase 1 study of patritumab deruxtecan (cohorts 1 and 3a). Extended follow-up data from the dose escalation portion and dose expansion cohort 1 of the study were recently presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting and published in Cancer Discovery. This is the first BTD for patritumab deruxtecan and the seventh BTD across Daiichi Sankyo’s oncology portfolio. 2 “The Breakthrough Therapy Designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We are proud that the FDA has once again recognized our innovative science and technology and we look forward to bringing this potential first-in-class HER3 directed antibody drug conjugate to patients with this specific type of lung cancer as quickly as possible.”
The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate (ORR) assessed by blinded independent central review. Secondary study endpoints include investigator-assessed ORR, safety and pharmacokinetics. The study enrolled patients at multiple sites in Asia, Europe and North America. For more information, visit ClinicalTrials.gov. About Patritumab Deruxtecan Patritumab deruxtecan (HER3-DXd) is one of three lead DXd ADCsin the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is comprised of a fully human anti-HER3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload (an exatecan derivative, DXd) via a stable tetrapeptide-based cleavable linker. Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC. 4 Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.
For more information, please visit www.daiichisankyo.com.
DESTINY-Lung04 Phase 3 Trial of ENHERTU® Initiated in Patients with Previously Untreated HER2 Mutant Metastatic Non-Small Cell Lung Cancer Tokyo, Munich and Basking Ridge, NJ – (December 23, 2021) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that the first patient was dosed in the global DESTINY-Lung04 phase 3 trial evaluating the efficacy and safety of ENHERTU® (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), as a first-line treatment in patients with HER2 mutant unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). DESTINY-Lung04 is the first head-to-head trial in NSCLC evaluating ENHERTU as a first-line treatment compared to the standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation. Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths globally, with 80% to 85% classified as NSCLC. 1,2,3 There are currently no medicines approved specifically for the treatment of HER2 mutant NSCLC, which affects approximately 2% to 4% of patients with non-squamous NSCLC.4,5 Current standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC is PD-1 or PD-L1 immunotherapy with or without platinum-based chemotherapy.6 While these treatment regimens can improve survival in NSCLC, approximately 40% to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for additional treatment approaches. 7,8,9,10,11 “The results seen in the DESTINY-Lung01 trial showed a robust and durable tumor response in previouslytreated patients with HER2 mutant metastatic non-small cell lung cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Based on these promising findings, we are conducting DESTINY-Lung04 to evaluate the potential of ENHERTU as an earlier line of therapy in this patient population.” 2 About DESTINY-Lung04 DESTINY-Lung04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, nonsquamous NSCLC harboring a HER2 exon 19 or 20 mutation. Patients will be randomized 1:1 to receive either ENHERTU or standard of care. The primary endpoint of DESTINY-Lung04 is progression-free survival (PFS) as assessed by blinded independent central review (BICR). Secondary endpoints include overall survival, investigator-assessed PFS, overall response rate and duration of response as assessed by BICR and investigator, pharmacokinetics, patient-reported tolerability, immunogenicity and safety. DESTINY-Lung04 will enroll approximately 264 patients at multiple sites across Asia, Europe, and North America. For more information about the trial, visit ClinicalTrials.gov.
About ENHERTU ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed antibody drug conjugate (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 program 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 (5.4 mg/kg) is approved in more than 30 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. A supplemental New Drug Application is under review in Japan for the treatment of adult patients with HER2 positive unresectable or recurrent breast cancer previously treated with trastuzumab and a taxane, based on the results from the DESTINY-Breast03 trial. ENHERTU (6.4 mg/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. A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen. ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated 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 in the metastatic setting. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. • Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
For more information, please visit www.daiichisankyo.com.
Dec. 23, 2021 8:21 AM ET
By: Mamta Mayani, SA News Editor
Dec 22, 2021
– Leqvio® Becomes Fourth RNAi Therapeutic Approved by U.S. FDA and First and Only for Lowering LDL-C in Atherosclerotic Cardiovascular Disease (ASCVD) Which Can Affect Up to 30 Million Americans –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 22, 2021-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today highlighted the significance of the U.S. Food and Drug Administration’s (FDA) approval of Leqvio® (inclisiran), the fourth small interfering RNA (siRNA) therapy (or RNAi therapeutic) approved in the U.S., and the first and only to lower low-density lipoprotein cholesterol (also known as “bad cholesterol” or LDL-C). Leqvio is indicated in the U.S. as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. Alnylam scientists discovered inclisiran and published the first clinical data. Alnylam also supported early clinical development. As of January 2020, Novartis has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement. Novartis AG continues to develop inclisiran and commercialize Leqvio worldwide, with Alnylam eligible to receive tiered royalties between 10 and 20 percent on global sales.
Leqvio is the fourth Alnylam-discovered medicine using its RNAi therapeutic platform to be approved to date. The Leqvio approval marks the first U.S. approval of an RNAi therapeutic indicated to treat a major risk factor for a highly prevalent disease. Alnylam launched its first RNAi therapeutic in 2018 with the FDA approval of ONPATTRO® (patisiran) for treatment of the polyneuropathy caused by hATTR amyloidosis, a progressive and life-threatening, rare, genetic disease. Leqvio was approved to lower LDL cholesterol and has the potential to benefit millions of people with ASCVD and also those with HeFH around the world.
“The approval of Leqvio, a potentially transformational medicine for lowering LDL-C is a historic event for Alnylam and its RNAi therapeutics platform. The demonstrated ability of Leqvio to lower LDL cholesterol up to 52% versus placebo on top of maximally tolerated statins with just two doses per year after an initial dose and another at three months represents a breakthrough that carries the potential to treat millions of people with ASCVD who are struggling to control elevated LDL cholesterol,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “More broadly, we believe the approval of Leqvio validates the future potential of RNAi therapeutics in large population diseases, and facilitates Alnylam’s advancement toward its bold Alnylam P5x25 strategy and goals. We are proud to share in the significance of this milestone with Novartis who made this approval a reality.”
History of Leqvio (inclisiran)
Inclisiran was discovered by Alnylam and, in collaboration with The Medicines Company, advanced into clinical development in 2014. Upon successful completion of Phase 1 clinical studies, the ORION clinical program was launched in 2015. The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, where all of the 3,457 participants with ASCVD or HeFH had elevated LDL-C while being on a maximally tolerated dose of statin therapy. This comprehensive Phase 3 program represents the largest clinical program conducted to date for an investigational RNAi therapeutic program. Two complementary Phase 3 cardiovascular outcomes trials, ORION-4 and the Novartis initiated VICTORION-2-PREVENT are currently ongoing.
“We believe that the creation of Leqvio was made possible by the development of our ESC-GalNAc conjugate delivery platform,” said Kevin Fitzgerald, Ph.D., Chief Scientific Officer of Alnylam, and scientist who led the initial development of Leqvio at Alnylam. “The U.S. approval of Leqvio will bring RNAi therapeutics to even more patients with elevated or inadequately controlled LDL-C. Moreover, this approval highlights the potential for additional Alnylam RNAi therapeutic programs in prevalent disease indications.”
In the U.S., Leqvio is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia HeFH or clinical ASCVD, who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined.
The European Medicines Agency (EMA) granted inclisiran marketing authorization in December 2020 for adults with primary hypercholesterolaemia (heterozygous familial and non‑familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid‑lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid‑lowering therapies in patients who are statin‑intolerant, or for whom a statin is contraindicated. Leqvio has now been approved in more than 50 countries.
As part of Alnylam’s strategic financing agreement with Blackstone, a leading private equity firm, 50 percent of Leqvio-related Alnylam royalties will flow to Blackstone.
For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211221005519/en/
Alnylam Pharmaceuticals, Inc.
Source: Alnylam Pharmaceuticals, Inc.
Dec. 22, 2021 4:47 PM ET
By: Dulan Lokuwithana, SA News Editor
WALTHAM, Mass., Dec. 22, 2021 /PRNewswire/ -- Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that the European Commission has granted Orphan Drug Designation to SNDX-5613, the Company's highly selective oral menin inhibitor, for the treatment of acute myeloid leukemia (AML).
"Supported by a growing body of clinical data, we firmly believe that SNDX-5613 is ideally positioned to serve as a best-in-class, meaningful intervention for patients with NPM1 and MLLr acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Receipt of Orphan Drug Designation from the European Commission further validates the important role that SNDX-5613 could play in the treatment of this highly underserved patient population, and we are fully committed to ensuring that it is able to reach as many of these patients as possible."
The European Commission grants Orphan Drug Designation for medicinal products intended to treat life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 people in the European Union (EU) and when no satisfactory method of diagnosis, prevention, or treatment of the condition can be authorized. The designation provides certain benefits and incentives in the EU, including protocol assistance, fee reductions, and ten years of market exclusivity once the medicine is on the market.
SNDX-5613 was previously granted Orphan Drug Designation for the treatment of adult and pediatric AML by the U.S. Food and Drug Administration.
SNDX-5613 is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged (MLLr) acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. In preclinical models of MLLr acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company's AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Commission for the treatment of patients with AML, and Fast Track designation by the U.S. FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a mixed lineage leukemia rearranged MLLr or NPM1 mutation.
For more information, please visit www.syndax.com or follow the Company on Twitter and LinkedIn.
View original content:https://www.prnewswire.com/news-releases/syndax-announces-orphan-drug-designation-granted-to-sndx-5613-by-european-commission-for-the-treatment-of-acute-myeloid-leukemia-301449487.html
SOURCE Syndax Pharmaceuticals, Inc.
Dec. 22, 2021 7:35 AM ET
By: Mamta Mayani, SA News Editor
December 21, 2021 8:56am EST
FDA also allows integrated or meta-analysis of the previous trial results in CD20 final analysis
CD20 is allowed to have four dosages of leronlimab in the first four weeks via IV infusion
VANCOUVER, Wash.--(BUSINESS WIRE)-- CytoDyn Inc. (OTCQB: CYDY) (“CytoDyn” or the “Company”), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, today announced that it has received a positive response from the U.S. Food and Drug Administration (“FDA”) to conduct a Phase 3, randomized, double blind, placebo controlled trial to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia with need for Invasive Mechanical Ventilation ("IMV”) or Extracorporeal Membrane Oxygenation (“ECMO”).
The submission of this protocol was previously announced on December 9th. Patients in this trial will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab with standard of care or placebo with standard of care administered via IV infusion weekly over a four-week treatment period (dosage on days 0, 7, 14, and 21).
Nader Pourhassan, Ph.D., CytoDyn’s President and Chief Executive Officer, commented, “As COVID-19 cases continue to surge in the U.S., we are grateful for the opportunity to move forward with the Phase 3 trial of leronlimab as a treatment option for critically ill COVID-19 patients. There continues to be an immense need for therapeutic options to support this population, and we are optimistic that Phase 3 will show promising results. In previous trials we had issues with our CRO that we now have overcome, and are very excited that the FDA in their recent communication with CytoDyn have stated, ‘As there are now several completed, ongoing, or planned randomized trials of PRO140 (leronlimab) that include severe or critical hospitalized COVID-19 patients, any integrated or meta-analysis would be strengthened if you prespecified analysis details and submitted these for review before results of ongoing or planned trials are Unblinded.’ Since the beginning of the current pandemic, leronlimab has received about 100 eINDs approved for leronlimab by the FDA for use in critically ill COVID-19 patients in the U.S., as a result of these FDA approved eINDs and strong results from most of them, physicians have published four papers in peer review journals. Meanwhile leronlimab was also used in Philippines, under compassionate Special Permit for a fee by over 240 patients with very high rate of success. All these accomplishments along with our current trials in Brazil, we are very hopeful that we will be part of the solution to the current pandemic in U.S. and abroad especially in the critically ill population. We look forward to working with the FDA to expand the access to leronlimab as the fight against COVID-19 continues.”
The U.S. Food and Drug Administration (FDA) granted CytoDyn Fast Track designation to explore two potential indications using leronlimab to treat Human Immunodeficiency Virus (HIV) and metastatic cancer. The first indication is combination therapy with HAART for HIV-infected patients, and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor important in HIV infection, tumor metastases, and other diseases, including nonalcoholic steatohepatitis (NASH). Leronlimab has been studied in 16 clinical trials involving more than 1,200 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab combined with HIV standard care in patients with multi-drug resistance to current available classes of HIV drugs).
Leronlimab, among various potential applications, is a viral-entry inhibitor in HIV/AIDS. It binds to CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab does not work on other strains of HIV (for example X4), however, R5 is the most dominant strain of HIV. Five clinical trials have demonstrated leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent with fewer side effects and less frequent dosing requirements than currently used daily drug therapies. Cancer research has shown CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control (for example, through angiogenesis). Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 97% in a murine xenograft model. As a result, CytoDyn is conducting two clinical trials, one, a Phase 2 in mTNBC, which was granted Fast Track designation by the FDA in 2019, and a second, a Phase 2, basket trial which encompasses 22 different solid tumor cancers.
The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation. After completing two clinical trials with COVID-19 patients (a Phase 2 and a Phase 3), CytoDyn initiated a Phase 2 investigative trial for post-acute sequelae of SARS COV-2 (PASC), also known as COVID-19 Long-Haulers. This trial evaluated the effect of leronlimab on clinical symptoms and laboratory biomarkers to further understand the pathophysiology of PASC. It is currently estimated that between 10-30% of those infected with COVID-19 develop long-term sequelae. Common symptoms include fatigue, cognitive impairment, sleep disorders, and shortness of breath. CytoDyn plans to pursue clinical trials to evaluate leronlimab’s effect on immunological dysregulation in other post-viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab. There are currently no FDA approved treatments for NASH, which is a leading cause of liver transplant. About 30 to 40 percent of adults in the U.S. live with NAFLD, and 3 to 12 percent of adults in the U.S. live with NASH. There have been no strong safety signals identified in patients administered leronlimab in multiple disease spectrums, including patients with HIV, COVID-19, and oncology.
More information is at www.cytodyn.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211221005432/en/
Source: CytoDyn Inc.
Released December 21, 2021
Dec. 21, 2021 9:28 AM ET
Dec. 20, 2021 12:18 PM ETBy: Jonathan Block, SA News Editor
adeno-associated virus serotype 5 (AAV5) vector containing the hSERPING cDNA sequence encoding human C1-esterase inhibitor (C1-INH)
bluebird bio Announces FDA Priority Review of Biologics License Application for eli-cel Gene Therapy for Cerebral Adrenoleukodystrophy (CALD) in Patients Without a Matched Sibling Donor
If approved, eli-cel will be the first and only gene therapy for the treatment of CALD, a rare neurodegenerative disease primarily affecting young children that can lead to progressive, irreversible loss of neurologic function and death
FDA set PDUFA date of June 17, 2022
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 17, 2021--
bluebird bio, Inc. (Nasdaq: BLUE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for elivaldogene autotemcel (eli-cel, Lenti-D®), the company’s gene therapy for cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age. Eli-cel is an investigational one-time gene therapy, custom-designed to treat the underlying cause of this irreversible neurodegenerative disease and to stabilize neurologic function. The agency set a Prescription Drug User Fee Act (PDUFA) goal date of June 17, 2022.
“Eli-cel is an important potential therapeutic option for patients with CALD—a devastating neurodegenerative disease—and we are encouraged to be moving forward given the urgent unmet need for these children and their families,” said Andrew Obenshain, chief executive officer, bluebird bio. “As the second BLA acceptance for bluebird bio this year, this is a meaningful milestone in our work to deliver one-time treatments for severe genetic diseases.”
If approved, eli-cel will be the first approved treatment to address the underlying genetic cause of disease for patients living with CALD in the U.S. – offering appropriate patients an alternative to allogeneic hematopoietic stem cell transplant (allo-HSCT), which is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. It is estimated that more than 70% of patients diagnosed with CALD do not have a matched sibling donor.
The BLA for eli-cel is supported by efficacy and safety data from the completed Phase 2/3 Starbeam study (ALD-102) (N=32). Additionally, the BLA contains data for 23 subjects dosed in the Phase 3 ALD-104 study. Study ALD-104 has subsequently completed enrollment and follow-up is ongoing. All patients who completed ALD-102, as well as those who will complete ALD-104, are invited to participate in a long-term follow-up study (LTF-304).
In ALD-102, 90.6% (29/32) of patients met the primary endpoint of Major Functional Disabilities (MFD)-free survival at 24 months. As previously reported, two patients withdrew from study ALD-102 at investigator discretion, and one additional subject experienced rapid disease progression early in the study, resulting in MFDs and subsequent death. All patients who completed ALD-102 enrolled in follow-up study LTF-304. The median duration of follow-up is 3.5 years (42.3 months; 13.4, 83.7).
Adverse reactions attributed to eli-cel observed in clinical trials include myelodysplastic syndrome, cystitis viral, pancytopenia, and vomiting. There have been no reports of graft-versus-host-disease, graft failure or rejection, transplant-related mortality, or replication competent lentivirus in the 55 patients who received eli-cel in clinical studies (ALD-102/LTF-304 and ALD-104).
On August 9, bluebird bio announced that the eli-cel clinical program was placed on a clinical hold, following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS). Available evidence suggests that the event was likely mediated by Lenti‑D lentiviral vector (LVV) insertion. Consistent with this known risk, two additional cases of MDS have subsequently been reported and details have been shared with the FDA and study investigators. The FDA clinical hold for eli-cel is ongoing and all patients who received eli-cel in the clinical program continue to be closely monitored, per study protocols. Given the devastating and fatal nature of CALD and lack of other treatment options for patients without a matched sibling donor, bluebird bio continues to assess the overall benefit/risk profile of the product as favorable for patients with CALD who do not have a matched sibling donor.
The FDA’s Priority Review designation is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions, and targets a review timeline of six months after the 60-day FDA BLA filing decision, compared to a standard review timeline of 10 months after the 60-day FDA filing decision.
The FDA previously granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation.
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that primarily affects males; worldwide, an estimated one in 21,000 male newborns are diagnosed with ALD. The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently leads to toxic accumulation of very long-chain fatty acids (VLCFAs), primarily in the adrenal gland and white matter of the brain and spinal cord. Approximately 40% of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7). Early diagnosis and treatment of CALD is essential, as nearly half of patients who do not receive treatment die within five years of symptom onset.
About elivaldogene autotemcel (eli-cel, Lenti-D®) gene therapy
eli-cel uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which is thought to facilitate the breakdown of very long-chain fatty acids (VLCFAs). The expression of ALDP and effect of eli-cel is expected to be life-long. The goal of treatment with eli-cel is to stop the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with eli-cel, there is no need for donor HSCs from another person.
bluebird bio’s clinical development program for eli-cel includes the completed pivotal Phase 2/3 Starbeam study (ALD-102) and the ongoing Phase 3 ALD-104 study, which has completed enrollment. Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have received eli-cel for CALD and completed two years of follow-up in ALD-102 or ALD-104. Clinical studies of eli-cel are currently on hold with the FDA.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211217005659/en/
Source: bluebird bio, Inc.
New and Updated Data Demonstrating Sustained Treatment Response in Patients Treated in Largest Sickle Cell Gene Therapy Program To-Date Presented at ASH21 and Published in NEJM
Updated data from the pivotal cohort of HGB-206 reinforce that optimized manufacturing and treatment processes are associated with improved biologic and clinical outcomes, including stable production of gene therapy-derived anti-sickling hemoglobin and continued complete resolution of severe VOEs up to 36 months follow-up (n=2)
Patient-reported data on health-related quality of life (HRQoL) complement clinical findings and the strongest HRQoL improvements in any sickle cell gene therapy program
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 12, 2021-- bluebird bio, Inc. (NASDAQ: BLUE) today announced updated results from its Phase 1/2 HGB-206 study of lovotibeglogene autotemcel (lovo-cel; formerly LentiGlobin® for SCD, bb1111) gene therapy for sickle cell disease, including further analyses from its pivotal cohort, HGB-206 Group C, following enhancements to the manufacturing protocols and treatment process. In addition to continued complete resolution of severe vaso-occlusive events (VOEs), patients in Group C achieved near normal levels of key hemolysis markers and experienced sustained improvements in patient-reported quality of life following treatment. Data were presented in two oral sessions at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 11-14, 2021, at the Georgia World Congress Center in Atlanta and virtually; select data from the Group C cohort of the HGB-206 study were simultaneously published in The New England Journal of Medicine (NEJM).
“Data presented at ASH and published today in The New England Journal of Medicine affirm that this lentiviral gene transfer for sickle cell disease has the potential to improve the day-to-day reality of people living with sickle cell disease by eliminating the disruptive, painful crises that can occur multiple times per month,” said John F. Tisdale, MD, Chief, Cellular and Molecular Therapeutics Branch, NHLBI, Bethesda, Md. “Sickle cell is a complex and often misunderstood disease that is associated with more symptoms and long-term effects than pain alone. It is encouraging to see that the treatment fundamentally impacted the pathophysiology of patients’ disease through the sustained production of vector-derived anti-sickling hemoglobin to substantially reduce sickling and hemolysis.”
Clinical studies evaluating lovo-cel in sickle cell disease represent the largest sickle cell disease gene therapy data set to date. As of February 17, 2021, 49 patients have been treated with lovo-cel with up to six years of patient follow-up (median: 24 months) across the HGB-205 (n=3), HGB-206 (n=44) and HGB-210 (n=2) clinical studies, representing more than 109 total patient-years of data. The Phase 1/2 HGB-206 trial includes Groups A (n=7), B (n=2) and C (n=35), reflecting progressive adaptations to the treatment and manufacturing processes.
Sickle cell disease is a serious, progressive and debilitating genetic disease caused by a single mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs requiring frequent hospitalization. In the U.S., the median age of death for someone with sickle cell disease is 43-46 years. Additionally, one in four people living with sickle cell disease experience a stroke by age 45.
In the HGB-206 study, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.
lovo-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their RBCs can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, thereby reducing sickled RBCs, hemolysis and other complications.
“The remarkable depth and breadth of data presented at ASH and published in The New England Journal of Medicine distinctively demonstrates the impact of lovo-cel on biologic and clinical outcomes, as well as to patient-reported outcomes that indicate a meaningful difference in the daily lives of people with sickle cell disease,” said Richard Colvin, MD, PhD, Chief Medical Officer, bluebird bio. “The ability to trace how lovo-cel integrates on a genetic level is a distinguishing characteristic of LVV gene therapy and confers a unique understanding of how the proposed mechanism of action of the drug product is correlated to safety and clinical outcomes.”
Data published in The New England Journal of Medicine is titled Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease Gene Therapy.
Updated HGB-206 Group C Efficacy & Safety Data
As of February 2021, the 35 Group C patients had up to 37.6 months of follow-up (median of 17.3; min-max: 3.7-37.6 months), for a total of 54.8 patient-years of experience.
Following engraftment, median total hemoglobin increased from 8.5 g/dL at baseline to ≥11 g/dL from six through up to 36 months post-infusion in all patients; notably, sickle hemoglobin (HbS) in all patients was less than 60% of total hemoglobin, and gene therapy-derived anti-sickling hemoglobin, HbAT87Q, contributed at least 40% of total hemoglobin.
These decreased levels of sickle hemoglobin (HbS) after lovo-cel infusion were comparable to individuals living with sickle trait (βS/βA), not in the study—in general, people with sickle cell trait enjoy normal life spans with no medical problems related to sickle cell trait.
All evaluable patients (n=25) continued to experience complete resolution of severe VOEs through up to 36 months of follow-up, compared with a median of 3.5 per year (min-max: 2.0-13.5) in the 24 months before enrollment.
HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of lovo-cel gene therapy for sickle cell disease that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=35). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received lovo-cel made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.
Under a Cooperative Research and Development Agreement (CRADA), the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, assisted bluebird in conducting clinical trials of its investigational LentiGlobin® gene therapy.
About lovotibeglogene autotemcel (lovo-cel; formerly LentiGlobin® for SCD, bb1111)
lovotibeglogene autotemcel (lovo-cel) gene therapy is an investigational one-time treatment being studied for sickle cell disease (SCD), that is designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells (RBCs) can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled RBCs, hemolysis, and other complications. bluebird bio’s clinical development program for lovo-cel includes the completed Phase 1/2 HGB-205 and ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio sponsored clinical studies of lovo-cel.
As of February 17, 2021, a total of 49 patients have been treated with lovo-cel, with up to six years of patient follow-up, in the HGB-205 (n=3), HGB-206 (n=44), and HGB-210 (n=2) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2), and C (n=35), representing progressive adaptations to the manufacturing and treatment and processes. In the Group C cohort of the Phase 1/2 HGB-206 study, no severe vaso-occlusive events (VOEs) were reported with up to 24 months of follow-up in patients with a history of at least four severe VOEs and at least six months of follow-up.
The safety data profile remains generally consistent with the risks of autologous stem cell transplantation and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to lovo-cel. There were no serious AEs related to lovo-cel.
In the Group C cohort of the HGB-206 study, one patient with underlying cardiopulmonary disease and SCD-related complications died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to lovo-cel.
In the initial cohort (Group A) of the HGB-206 study, two patients treated with lovo-cel developed acute myeloid leukemia (AML). After thorough investigations into the cases, bluebird bio determined that these were unlikely related to the insertion of bluebird’s lentiviral vector (LVV) gene therapy for SCD.
For more information on lovo-cel studies, visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov.
The FDA has granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation, and rare pediatric disease designation for lovo-cel.
lovo-cel is investigational and has not been approved in any geography.
LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211212005093/en/
Source: bluebird bio, Inc.
Dec. 13, 2021 8:41 AM ET
By: Mamta Mayani, SA News Editor
December 12, 2021Download PDF
INDIANAPOLIS, Dec. 12, 2021 /PRNewswire/ -- Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), today announced updated clinical data from the pirtobrutinib global Phase 1/2 BRUIN clinical trial in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL). Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor. These data are being presented in oral presentations at the 2021 American Society of Hematology (ASH) Annual Meeting (abstracts 391 and 381).
"BRUIN is now the largest clinical trial conducted to date that has enrolled CLL/SLL patients previously treated with modern standards of care including BTK and BCL2 inhibitors. In this real-world population of relapsed/refractory patients, pirtobrutinib continues to demonstrate robust activity with a safety profile amenable to chronic administration. Now with the longer follow-up that this analysis affords, we are encouraged by evidence of durable disease control in this very heavily pretreated CLL/SLL population," said Anthony Mato, M.D., MSCE, director of the CLL Program at Memorial Sloan Kettering Cancer Center and a presenting author. "As recently detailed by a global panel of experts in Clinical Cancer Research, there are currently no evidence-based treatment options for patients following covalent BTK and BCL2 inhibitor therapy. Pirtobrutinib has the potential to offer a meaningful new approach for these CLL/SLL patients, as well as those patients who are less heavily pretreated."
"I'm pleased to share the pirtobrutinib data in MCL patients with the hematology community at ASH", said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center and a presenting author. "Since our last analysis of these data, we have doubled the number of evaluable BTK pretreated patients and observed a nearly-identical response rate. New treatment options following covalent BTK therapy represent an area of urgent unmet need and the durable response rate observed with pirtobrutinib demonstrates its potential to provide a significant clinical advancement for patients with MCL following covalent BTK therapy."
Key Data Presented at ASH
As of July 16, 2021, 618 patients were enrolled in the study, including 296 with CLL/SLL, 134 with MCL, and 188 with other B-cell malignancies. The efficacy data presented at ASH are based on investigator response assessments. Patients were considered efficacy-evaluable if they had at least one post-baseline response assessment or if they discontinued treatment prior to their first post-baseline response assessment.
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Among the 296 CLL/SLL patients enrolled, 261 were previously treated with a BTK inhibitor and are the subject of this analysis. The median number of prior lines of therapy was three with 100% receiving a prior BTK inhibitor, 88% an anti-CD20 antibody, 79% chemotherapy, 41% venetoclax, 20% a PI3K inhibitor, 6% CAR-T therapy and 2% stem cell transplant.
In 252 efficacy-evaluable patients (an additional nine patients ongoing prior to first restaging), 171 responded including two complete responses (CR), 137 partial responses (PR), 32 partial responses with ongoing lymphocytosis (PR-L), and 62 stable disease (SD), resulting in an overall response rate (ORR) of 68% (95% CI: 62-74). Responses continue to deepen over time, with the ORR rising to 73% (88/119) for those followed 12 months or more, and ORR remains consistent regardless of reason for prior BTK discontinuation, type or number of prior therapies or BTK C481 or PCLG2 mutational status.
Pirtobrutinib demonstrated evidence of durable activity with a median progression-free survival (PFS) not reached in patients who had received at least a prior BTK inhibitor (lower limit of 95% confidence interval of 17.0 months, median of three prior lines of therapy). In patients who had received at least a BTK inhibitor and BCL2 inhibitor (median of five lines of prior therapy), the estimated median PFS was 18 months, although these data remain immature and unstable due to the small percentage of patients with progression. As of the data cut-off, 74% (194/261) of BTK pre-treated patients remained on pirtobrutinib. Median follow-up for all BTK pre-treated patients was 9.4 months (range 0.3-27.4 months).
In an exploratory analysis in patients with prior progression on a BTK inhibitor, the PFS with pirtobrutinib was similar in patients with BTK C481-mutated and BTK C481-wildtype CLL and SLL.
Loxo Oncology at Lilly is studying pirtobrutinib in multiple Phase 3 studies. Details on the trials can be found in Trials in Progress posters (abstracts 2422, 3732, 3736 and 3742) and on lillyloxooncologypipeline.com.
About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available covalent BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email email@example.com.
About the BRUIN Phase 1/2 Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates pirtobrutinib as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin's lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The dose escalation phase followed a "3+3" design with pirtobrutinib dosed orally in 28-day cycles. As dose cohorts were cleared, additional patients could enroll in cleared cohorts and intra-patient dose escalation was permitted. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2 dose expansion, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).
About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY
Disclosure: Dr. Mato has provided consulting and advisory services to Loxo Oncology at Lilly and Eli Lilly and Company.
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SOURCE Eli Lilly and Company
December 12, 2021 at 9:00 AM ESTPDF Version
- No adverse events related to investigational SAR445136 were reported
- All four treated patients experienced increases in total hemoglobin, fetal hemoglobin and percent F cells; none required blood transfusions post engraftment
BRISBANE, Calif.--(BUSINESS WIRE)--Dec. 12, 2021-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary proof-of-concept clinical data from the Phase 1/2 PRECIZN-1 study of SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development with Sanofi for the treatment of sickle cell disease (SCD). These data are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA. The poster presentation, which includes follow-up data up to 91 weeks for the longest-treated patient, is available on Sangamo’s website in the Investors and Media section under Events and Presentations.
“We are very pleased with these updated preliminary proof-of-concept efficacy and safety results, which we believe illustrate the therapeutic potential of zinc finger nuclease engineered cell therapy to address the current unmet needs of patients with sickle cell disease,” said Rob Schott, M.D., M.P.H, F.A.C.C, Head of Development at Sangamo. “We believe this is an important demonstration of our versatile zinc finger platform translating meaningfully into the clinic.”
As of the September 22, 2021 cutoff date, the most recently treated patient in the PRECIZN-1 Phase 1/2 study had been followed for 26 weeks and the longest-treated patient had been followed for 91 weeks. None of the four treated patients required blood transfusions post engraftment. Total hemoglobin stabilized by Week 26 after treatment with SAR445136 in all four patients. Fetal hemoglobin level increased from 0.1-11% at screening to 14-39% by Week 26 in all four patients and was 38% in the longest-treated patient at 91 weeks. Percent F cells increased to 64-96% by 39 weeks of follow-up in all four patients, persisting at 99% in the patient with 91 weeks of follow-up. The SAR445136 investigational drug product had on-target BCL11A gene modification (61-78%) in all four patients.
“These preliminary proof of concept efficacy and safety results support the potential therapeutic value of the zinc finger nuclease-mediated modification of the BCL11ESE region,” said Karin Knobe, Head of Development, Rare Diseases and Rare Blood Disorders at Sanofi.
As of the cutoff date, there were no adverse events (AEs) assessed as related to SAR445136. Most AEs reported in the screening, mobilization, apheresis and conditioning periods were SCD-related events. One serious adverse event of sickle cell anemia with crisis (vaso-occlusive crisis or VOC) was reported approximately nine months after treatment with SAR445136 in one patient, and no other SCD-related events were reported in the four patients post-infusion.
Additional data from this study are expected to be presented at a medical meeting in 2022.
About the PRECIZN-1 study
PRECIZN-1 is an ongoing first-in-human, open label, single arm, multi-site Phase 1/2 study in up to eight patients with SCD evaluating the safety and tolerability of cell therapy candidate SAR445136. The therapeutic product is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology targeting the BCL11a gene erythroid-specific enhancer (ESE) to increase endogenous fetal hemoglobin (HbF) production. SAR445136 has received Fast Track Designation from the FDA and Orphan Medicinal Product from the EMA. The safety and efficacy of SAR445136 has not been reviewed by any regulatory authority worldwide.
For more information about Sangamo, visit www.sangamo.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211212005050/en/
Source: Sangamo Therapeutics, Inc.
Dec. 13, 2021 3:06 AM ET
By: Mamta Mayani, SA News Editor
December 12, 2021 at 4:30 PM ESTPDF Version
NEW YORK & BRISBANE, Calif.--(BUSINESS WIRE)--Dec. 12, 2021-- Pfizer Inc. (NYSE: PFE) and Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A. The Alta study data, in patients with severe hemophilia A, are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA. The oral presentation slides, which include follow-up data up to 195 weeks for the longest-treated patient, are available on Sangamo’s website in the Investors and Media section under Events and Presentations.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211212005051/en/
At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate (ABR) was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up as of the October 1, 2021 cutoff date. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort have resumed prophylaxis.
“These latest results further suggest the potential of this investigational therapy to bring transformational benefit to eligible patients living with severe hemophilia A, if confirmed in ongoing clinical trials,” said Seng H. Cheng, Senior Vice President and Chief Scientific Officer, Pfizer Rare Disease.
“We continue to be encouraged by findings from the Phase 1/2 Alta study in patients with severe hemophilia A,” said Rob Schott, M.D., M.P.H, F.A.C.C, Head of Development at Sangamo. “We believe these two-year results demonstrate the potential of this gene therapy candidate to minimize significant symptoms associated with hemophilia A and become an alternative to the current burden of disease management.”
Giroctocogene fitelparvovec was generally well-tolerated in this Phase 1/2 study. Among the five patients in the highest dose cohort, four received corticosteroids for liver enzyme (ALT/AST) elevations. All elevations fully resolved with oral corticosteroids. As previously reported, one patient in the highest dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec and resolved approximately 12 hours post-infusion. Across all four cohorts, 26 treatment-related adverse events occurred in six patients as of the October 1, 2021 cutoff date. No other treatment-related serious adverse events were reported as of the cutoff date. Additionally, no confirmed FVIII inhibitor development occurred, and no thrombotic events were reported.
The Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec in patients with hemophilia A has started and is over 50% enrolled. Following the observation of FVIII levels greater than 150% in some treated patients, Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment to provide clinical management guidance for elevated FVIII levels. Subsequently, on November 3, 2021, the U.S. Food and Drug Administration (FDA) informed Pfizer that this trial has been placed on clinical hold while the protocol amendment and associated documents are reviewed.
About the Alta Study
The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The mean age of the 11 male patients assessed across four dose cohorts (9e11 vg/kg - 2 patients, 2e12 vg/kg - 2 patients, 1 e13 vg/kg - 2 patients and 3e13 vg/kg - 5 patients) is 30 years (range 18-47 years). Patients in this study will be assessed every six months until they enroll in a long-term follow-up study.
About the AFFINE study
The Phase 3 AFFINE (NCT04370054) study is an open-label, multicenter, single arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. Eligible study participants will have completed at least six months of routine FVIII prophylaxis therapy during the lead-in Phase 3 study (NCT03587116) in order to collect pretreatment data for efficacy and selected safety parameters.
The primary endpoint is impact on annualized bleeding rate (ABR) through 12 months following treatment with giroctocogene fitelparvovec. This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 12 months following infusion of giroctocogene fitelparvovec.
About giroctocogene fitelparvovec
The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency. Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer. Giroctocogene fitelparvovec is currently being studied in the Phase 3 AFFINE study.
For more information about Sangamo, visit www.sangamo.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211212005051/en/
Source: Sangamo Therapeutics, Inc.
Dec. 13, 2021 2:39 AM ET
By: Mamta Mayani, SA News Editor
Friday, Dec 10, 2021
South San Francisco, CA -- December 10, 2021 --
Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced new follow-up efficacy, safety and patient-reported outcomes (PROs) data from the Phase II CITYSCAPE trial, investigating the novel anti-TIGIT cancer immunotherapy tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone as an initial (first-line) treatment for people with PD-L1-positive metastatic non-small cell lung cancer (NSCLC). The full results are being featured as an oral presentation in the Proffered Paper session 2 (Abstract LBA2) at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2021, taking place December 8-11.1
“These encouraging results suggest that combining anti-TIGIT and anti-PD-L1 cancer immunotherapies such as tiragolumab and Tecentriq could potentially represent a novel approach to address unmet needs in cancer,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “With tiragolumab, we have the largest and most advanced anti-TIGIT clinical program, and we look forward to the results of our Phase III trials in lung cancer and other challenging tumor types.”
After 2.5 years median follow-up, tiragolumab plus Tecentriq continued to show an improvement in the intention-to-treat (ITT) population (n=67), driven by the PD-L1-high population (TPS ≥ 50%) (n=29). In the ITT population, the combination reduced the risk of disease worsening or death (progression-free survival; PFS) by 38% (median PFS=5.6 vs. 3.9 months; hazard ratio [HR]=0.62, 95% CI: 0.42–0.91) and improved overall response rates (ORR) (38.8% vs. 20.6%) compared with Tecentriq alone. A predefined exploratory analysis in the PD-L1-high population showed a 71% reduction in the risk of disease worsening or death (median PFS=16.6 vs. 4.1 months; HR=0.29, 95% CI: 0.15–0.53) and a clinically meaningful improvement in ORR (69% vs. 24.1%) with the combination compared with Tecentriq alone.1
The analysis also showed that tiragolumab plus Tecentriq improved overall survival (OS), a secondary endpoint of the study, in the ITT population, which was driven by the PD-L1-high population. After 2.5 years median follow-up, median OS was 23.2 vs. 14.5 months (HR=0.69, 95% CI: 0.44–1.07) in the ITT population. The exploratory data in the PD-L1-high population showed a clinically meaningful OS improvement. The median was not reached for the tiragolumab regimen and is projected to be greater than 30.3 months based on the lower confidence interval (NE [30.3-NE] vs. 12.8 months [4.7-24.2]; HR=0.23, 95% CI: 0.10-0.53).1
Data suggest that the combination was generally well-tolerated, showing similar rates of Grade 3-4 treatment-related adverse events (AEs) when adding tiragolumab to Tecentriq compared with Tecentriq alone (22.4% vs. 25%). The most common all cause AEs (rate greater than 5% difference between study groups) seen with the combination were infusion-related reactions, stiffness, dry skin, fatigue and rash. After longer follow-up, no new safety signals were observed with the combination. Patients generally reported minimal-to-moderate symptoms and generally maintained their quality of life compared with the start of treatment. PRO data from this exploratory analysis showed that lung symptoms, such as dyspnea and pain, did not appear to deteriorate with the addition of tiragolumab to Tecentriq.1
The CITYSCAPE study forms the basis of an industry-leading development program across multiple settings and tumor types.3 The Phase III SKYSCRAPER-01 trial is currently ongoing to confirm these results in the PD-L1-high population, with the goal of bringing this treatment option to patients. Earlier this year, tiragolumab was granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration – representing the first anti-TIGIT therapy to be granted this designation and the 37th BTD for Genentech’s portfolio of medicines. Since 2020, Genentech has initiated five Phase III trials evaluating tiragolumab plus Tecentriq in early and metastatic disease in lung (SKYSCRAPER-01, SKYSCRAPER-02, SKYSCRAPER-03) and esophageal cancers (SKYSCRAPER-07, SKYSCRAPER-08). Tiragolumab is also being evaluated in other solid tumors as well as in hematological cancers.
About the CITYSCAPE study1
CITYSCAPE is a global Phase II, randomized and blinded study evaluating tiragolumab plus Tecentriq® (atezolizumab) compared with Tecentriq alone in 135 patients with first-line PD-L1-positive locally advanced, unresectable or metastatic non-small cell lung cancer. Patients were randomized 1:1 to receive either tiragolumab plus Tecentriq or placebo plus Tecentriq, until progressive disease or loss of clinical benefit. Co-primary endpoints are overall response rate (ORR) and progression-free survival (PFS). Secondary endpoints include safety, overall survival (OS) and patient-reported outcomes (PROs). PRO results were assessed with EORTC QLQ-C30, a questionnaire developed to assess the quality of life of people with cancer, administered at baseline and throughout study treatment.
Tiragolumab is a first-in-class novel immune checkpoint inhibitor with an intact Fc region. Tiragolumab selectively binds to TIGIT, a novel inhibitory immune checkpoint which suppresses the immune response to cancer. 1 Based on preclinical research, tiragolumab is thought to work as an immune amplifier with other cancer immunotherapies such as Tecentriq. 2 The TIGIT pathway is distinct but complementary to the PD-L1/PD-1 pathway. Dual blockade with tiragolumab and Tecentriq may help overcome immune suppression and restore the immune response. 1
About Tecentriq® (atezolizumab)
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1. Tecentriq is designed to bind to PD-L1 expressed on tumor cells and tumor-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the re-activation of T cells. Tecentriq may also affect normal cells.
Tecentriq U.S. Indications
Tecentriq is a prescription medicine used to treat adults with:
A type of lung cancer called non-small cell lung cancer (NSCLC).
It is not known if Tecentriq is safe and effective in children.
Please see http://www.Tecentriq.com for full Prescribing Information and additional Important Safety Information.
For more information visit http://www.gene.com/cancer-immunotherapy.
For additional information about the company, please visit http://www.gene.com.
December 10, 2021PDF Version
– Seventh Clinical Collaboration Represents Continued Execution on Strategy to Advance Nirogacestat in Combination with BCMA Therapies –
STAMFORD, Conn., Dec. 10, 2021 (GLOBE NEWSWIRE) -- SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced that the company has entered into a clinical trial collaboration agreement with AbbVie, Inc. to evaluate nirogacestat, SpringWorks’ investigational gamma secretase inhibitor, in combination with ABBV-383, AbbVie’s investigational CD3 bispecific antibody directed against B-cell maturation agent (BCMA), in patients with relapsed or refractory multiple myeloma.
Gamma secretase inhibition helps prevent the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase levels of membrane-bound BCMA and reduce levels of soluble BCMA, thereby helping to enhance the activity of BCMA-targeted therapies, including CD3 bispecific antibodies.1,2
“We continue to progress our strategy to evaluate nirogacestat in combination with BCMA therapies for patients with multiple myeloma and are delighted to enter into our seventh BCMA clinical collaboration. We look forward to working with AbbVie to study nirogacestat in combination with ABBV-383,” said Saqib Islam, Chief Executive Officer of SpringWorks. “Together with our industry-leading collaborators, our goal remains to meaningfully improve clinical outcomes for patients with multiple myeloma.”
Under the terms of the agreement, AbbVie will sponsor and conduct the Phase 1b study to evaluate the safety, tolerability, and preliminary efficacy of the combination in patients with relapsed or refractory multiple myeloma, and will assume all costs associated with the study, other than expenses related to the manufacturing of nirogacestat and certain expenses related to intellectual property rights. AbbVie and SpringWorks will also form a joint steering committee to manage the clinical study, which is expected to commence in the first half of 2022.
Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.
In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma.1,2 SpringWorks is evaluating nirogacestat as a BCMA potentiator and has seven collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies, three bispecific antibodies and a monoclonal antibody. SpringWorks has also formed research collaborations with Fred Hutchinson Cancer Research Center and Dana-Farber Cancer Institute to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA-directed therapies using a variety of preclinical multiple myeloma models.
Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.
For more information, visit www.springworkstx.com and follow @SpringWorksTx on Twitter and LinkedIn.
12/08/2021 at 6:00 PM ESTPDF Version
VANCOUVER, British Columbia--(BUSINESS WIRE)--Dec. 8, 2021-- Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, today announced new clinical data for the HER2-targeted bispecific antibody, zanidatamab, in heavily pretreated HER2-positive breast cancer. The data are being presented at the San Antonio Breast Cancer Symposium (SABCS) taking place in San Antonio, Texas and virtually, December 7-10, 2021. In addition, Zymeworks will present a Trial in Progress poster detailing the ongoing clinical trial evaluating zanidatamab in combination with the CD47-blocker, evorpacept (ALX148).
Summary of Clinical Trial Results
The data presented at SABCS are from a clinical study of 24 patients with heavily pretreated HER2-positive metastatic breast cancer who received zanidatamab in combination with either vinorelbine (n=12), capecitabine (n=8), or paclitaxel (n=4). Patients received multiple prior regimens containing HER2-targeted agents including trastuzumab (96%), pertuzumab (96%), and T-DM1 (96%), and many also received a tyrosine kinase inhibitor.
In 22 efficacy-evaluable patients, treatment with zanidatamab and chemotherapy resulted in a cORR of 36.4% and DCR of 86.4%, and the majority of patients experienced a decrease in their tumor size. The mPFS is 7.3 months across all treatment regimens with 42% of patients still on study at the time of data cutoff. Zanidatamab in combination with single agent chemotherapy is well tolerated, with the majority of treatment-related adverse events considered mild to moderate in severity (Grade 1 or 2).
“Zanidatamab together with chemotherapy shows encouraging antitumor activity and a manageable safety profile in patients with HER2‑positive breast cancer that has progressed after treatment with multiple HER2-targeted agents,” said Neil Josephson, M.D., Chief Medical Officer at Zymeworks. “We were impressed by the activity and durability of disease control with zanidatamab, with over half of patients experiencing a confirmed response or stable disease lasting over 6 months. These results, together with data presented earlier this year in both HER2‑expressing biliary tract cancer and gastroesophageal adenocarcinoma, build on our belief that zanidatamab has the potential to be a foundational therapy across multiple HER2-expressing solid tumor indications. We look forward to sharing additional data with zanidatamab in HER2‑positive breast cancer from our other ongoing trials in the first half of 2022, including in combination with Ibrance and fulvestrant in late-line hormone receptor positive disease as well as in combination with docetaxel in the first-line setting.”
“Zanidatamab continues to generate clinical data that differentiate it from existing and emerging HER2-targeted standards of care,” said James Priour, Chief Commercial Officer at Zymeworks. “Expanding on our commitment to complete ongoing pivotal trials in biliary tract and gastric cancers, we see breast cancer as the next indication to pursue a potential label. As we await additional data in early lines of breast cancer, these data in late-line present an additional registrational opportunity. With the majority of HER2-positive breast cancer patients benefitting from new therapies and surviving longer than ever before, there is a significant commercial opportunity in the third- and fourth-line setting. We believe the data presented today demonstrate that zanidatamab and chemotherapy could be a new option for these patients.”
The following presentations are available to conference registrants on the SABCS conference website as well as to the general public at https://www.zymeworks.com/publications.
Zanidatamab in Combination with Chemotherapy in Late-Line HER2-Postive Breast Cancer – Clinical Results Presented Today
Title: Zanidatamab (ZW25), a HER2-targeted bispecific antibody, in combination with chemotherapy (chemo) for HER2-positive breast cancer (BC): Results from a phase 1 study.
Lead Author: Philippe L. Bedard, M.D., Princess Margaret Cancer Center, Toronto, ON Canada.
Program Number: P2-13-07
Zanidatamab is a bispecific antibody, based on Zymeworks’ Azymetric™ platform, that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. Zanidatamab’s unique binding properties result in multiple mechanisms of action including HER2-receptor clustering, internalization, and downregulation; inhibition of growth factor-dependent and -independent tumor cell proliferation; antibody-dependent cellular cytotoxicity and phagocytosis; and complement-dependent cytotoxicity. Zanidatamab is currently being evaluated in two pivotal clinical trials, one for the first-line treatment of advanced or metastatic HER2-positive gastroesophageal adenocarcinoma (HERIZON-GEA-01) and one for previously treated HER2-amplified biliary tract cancer (HERIZON-BTC-01). Zanidatamab is also being evaluated in several Phase 2 clinical trials for HER2 expressing gastroesophageal, colorectal, and breast cancers. The FDA has granted zanidatamab with Breakthrough Therapy designation for patients with previously treated HER2 gene-amplified biliary tract cancer, as well as two Fast Track designations, one as monotherapy for refractory biliary tract cancer and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma. These designations mean zanidatamab is eligible for Accelerated Approval, Priority Review and Rolling Review, as well as intensive FDA guidance on an efficient drug development program. Zanidatamab has also received Orphan Drug designations from the FDA as well as the European Medicines Agency for the treatment of biliary tract and gastric cancers.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211208006094/en/
Source: Zymeworks Inc.
Dec. 09, 2021 3:58 AM ET
12/09/2021 at 8:30 AM ESTPDF Version
VANCOUVER, British Columbia--(BUSINESS WIRE)--Dec. 9, 2021-- Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, today announced that its collaborator, BeiGene, Ltd., has dosed the first patient in South Korea in the HERIZON‑GEA‑01 trial. As a result of this development milestone, Zymeworks will receive a US$8 million payment under its zanidatamab collaboration agreement with BeiGene.
Zymeworks and BeiGene continue to work to expedite the opening of approximately 300 clinical trial sites across 38 countries in support of the global Phase 3 pivotal trial. With a 24-month projected enrollment period, this study may enable the submission of a supplemental Biologics License Application by Zymeworks in the United States as early as 2024.
Dec. 09, 2021 9:21 AM ET
By: Jonathan M Block, SA News Editor
Thu, 12/09/2021 - 11:00
Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) today announced that data from the Phase 2 expansion cohort (‘cohort 3’), exploring the triplet combination of monalizumab, cetuximab and durvalumab in the first-line treatment of patients with recurrent or metastatic head and neck squamous cell cancer (R/M HNSCC), will be presented virtually today at the ESMO Immuno-Oncology Congress 2021.
Monalizumab, Innate’s lead partnered asset, is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor-infiltrating cytotoxic CD8+ T cells and NK cells.
“These data show anti-tumor activity in the first study to evaluate this chemo-free triplet combination in first-line recurrent or metastatic head and neck cancer,” said Joyson Karakunnel, M.D., MSc, FACP, Chief Medical Officer of Innate Pharma. “We believe that the combination of monalizumab with the other two antibodies has the potential to become a new treatment option for patients. We look forward to collaborating with AstraZeneca on next steps of this program.”
After a median follow-up of 16.3 months, preliminary data suggest anti-tumor activity in the triplet of monalizumab, cetuximab and durvalumab in first-line treatment of R/M HNSCC.
As of August 1, 2021, 40 patients were enrolled. Thirteen patients had a confirmed response with a 32.5% overall response rate (95% confidence interval (CI): 20-48), including three complete responses. Seven out of 13 responders were still on treatment. Median duration of response was not yet reached (95% CI: 7.1-not available). The survival rate at 12 months was 58.6% (95% CI: 45-77) and the median overall survival was 15 months (95% CI: 11.4 - not available).
In addition, Innate performed an exploratory subgroup analyses (n=40) according to Combined Positive Score (CPS), which is a PD-L1 scoring method that helps predict response to anti-PD-(L)1 therapy. In this analysis, CPS>1 (n = 25), the subset that had the greatest number of patients, showed a 40% overall response rate (95% CI: 23-59) and median overall survival of 17.3 months (95% CI: 14.7-NA). There were 5 patients with CPS<1, and CPS was unavailable for 10 patients.
The safety of this chemotherapy free regimen was acceptable with a low rate of discontinuation.
The oral presentation (#123MO) entitled, “Monalizumab, cetuximab and durvalumab in first-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): a phase 2 trial,” will be presented from 12:15-12:20 pm CET today.
PARTENERED WITH ASTRAZENECA | PHASE 3 | HEAD AND NECK CANCER
Monalizumab (IPH2201) is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells.
Dec. 09, 2021 5:13 AM ET
By: Mamta Mayani, SA News Editor
Dec. 05, 2021 6:47 PM ETMesoblast Limited (MESO)GlobeNewswire
NEW YORK, Dec. 05, 2021 (GLOBE NEWSWIRE) -- Mesoblast Limited (MEOBF) (Nasdaq:MESO; ASX:MSB), global leader in allogeneic cellular medicines for inflammatory diseases, today provided new analyses from the landmark DREAM-HF Phase 3 trial showing that the greatest treatment benefit from rexlemestrocel-L is in HFrEF patients with diabetes and/or ischemia, who are at high-risk of cardiovascular mortality, heart attacks or strokes.
In recent guidance to Mesoblast, FDA confirmed that reduction in incidence of cardiovascular mortality or irreversible morbidity (non-fatal heart attack or stroke) is a clinically meaningful acceptable endpoint in patients with chronic HFrEF and encouraged Mesoblast to identify the highest-risk group with greatest likelihood of beneficial response to intervention with rexlemestrocel-L in the DREAM-HF Phase 3 trial.
In line with this guidance, Mesoblast performed additional analyses of MACE outcomes in pre-specified high-risk patient groups from the landmark DREAM-HF trial, and the results were presented December 3 by Chief Executive Dr Silviu Itescu at the 18th Global CardioVascular Clinical Trialists Forum (CVCT) in Washington DC.
The data showed that:
Diabetes Mellitus is not only a significant risk factor in the onset of heart failure, it also increases the risk of mortality and morbidity in patients who have existing heart failure.1-3 Type 2 diabetes causes structural heart disease and heart failure through myocardial ischemia involving small and large vessels. Importantly, inflammation which is a critical component of the pathophysiology of the disease is also known to accelerate large vessel atherosclerosis.1
The 3-point composite MACE is an endpoint the FDA has previously accepted for approval of multiple drugs to reduce cardiovascular risk in diabetic patients. FDA guidance states that reliance on a single study to provide the substantial evidence of effectiveness necessary to support a Biologic License Application (BLA) is generally limited to situations in which a trial has demonstrated a clinically meaningful effect on mortality, irreversible morbidity, or prevention of a disease with potentially serious outcome for which confirmation of the result with a second trial would be practically or ethically impossible. Mesoblast will submit for formal FDA review the new data analyses showing the reduction in mortality and irreversible morbidity by rexlemestrocel-L in HFrEF patients with diabetes and/or myocardial ischemia, to agree on a potential pathway to approval.
Mesoblast is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of late-stage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process.
Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide.
Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease and moderate to severe acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets.
Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
Source: Mesoblast Limited 2021 GlobeNewswire, Inc.
Dec. 06, 2021 5:10 AM ET
By: Mamta Mayani, SA News Editor
| 6 Dec 2021
— Recruitment of 687 patients globally completed in fifteen months, ahead of schedule —
— FRESCO-2 primary objective is to confirm overall clinical benefit seen in the China FRESCO pivotal study, and to support global registrations —
Hong Kong, Shanghai & Florham Park, NJ — Monday, December 6, 2021: HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM: HCM; HKEX: 13) today announces that it has completed patient enrollment of FRESCO-2, a Phase III registration study of fruquintinib, an investigational treatment for the treatment of patients with metastatic colorectal cancer (“CRC”) in the U.S., Europe, Japan and Australia. The enrollment goal was reached on December 2, 2021.
FRESCO-2 is a randomized, double-blind, placebo-controlled, multicenter trial being conducted in patients with metastatic CRC. The primary endpoint of the study is overall survival (“OS”). This large Phase III trial enrolled patients in over 150 sites in 14 countries. Additional details of the study may be found at clinicaltrials.gov, using identifier NCT04322539.
Dr. Marek Kania, EVP, Managing Director and Chief Medical Officer of HUTCHMED International Corporation, said, “HUTCHMED continues to execute on developing novel oncology medicines for patients worldwide despite the backdrop of the global pandemic. We would like to thank investigators, patients and their families for taking part in this study and we look forward to seeing the results of this study in patients with metastatic CRC, where there is a high unmet need for new treatment options.”
Topline results from the FRESCO-2 trial are expected to be reported in the second half of 2022 when the event-driven primary endpoint, OS, is mature. If positive, HUTCHMED would initiate plans to apply for marketing authorization of fruquintinib by the U.S. Food and Drug Administration (“FDA”), the European Medicines Agency (“EMA”) and the Japanese Pharmaceuticals and Medical Devices Agency (“PMDA”). The U.S. FDA granted Fast Track Designation for the development of fruquintinib for the treatment of patients with metastatic CRC in June 2020. Clinical data from the completed Phase III FRESCO study in Chinese patients, additional supporting studies in CRC and this FRESCO-2 global study, if positive, could support a future U.S. FDA New Drug Application (“NDA”) for the treatment of patients with advanced metastatic CRC (third-line and later). The FRESCO-2 study design was also reviewed and endorsed by the EMA and PMDA.
HUTCHMED retains all commercial rights to fruquintinib outside of China. In China, where fruquintinib is marketed under the brand name ELUNATE®, HUTCHMED is partnered with Eli Lilly and Company and is responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing. Fruquintinib is not approved for use outside of China.
Fruquintinib is a highly selective and potent oral inhibitor of VEGFR-1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.
Metastatic colorectal cancer in China: Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in late November 2018 under the brand name ELUNATE®. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. ELUNATE® is indicated for the treatment of patients with metastatic CRC who have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-EGFR therapy (RAS wild type). Results of the FRESCO study1, a Phase III pivotal registration trial of fruquintinib in 416 patients with metastatic CRC in China, were published in The Journal of the American Medical Association, JAMA, in June 2018 (clinicaltrials.gov identifier: NCT02314819).
Dec 01, 2021 DownloadPDF Format (opens in new window)
BURLINGAME, Calif.--(BUSINESS WIRE)-- Humanigen, Inc. (Nasdaq:HGEN) (“Humanigen”), a clinical-stage biopharmaceutical company focused on preventing and treating an immune hyper-response called ‘cytokine storm’ with its lead drug candidate, lenzilumab, announced today The Lancet Respiratory Medicine (“Lancet”), an internationally trusted, peer-reviewed source of clinical, public health, and global health knowledge, published positive results from Humanigen’s LIVE-AIR Phase 3 randomized, controlled trial of lenzilumab in hospitalized COVID-19 patients, as well as an independent expert commentary. The Lancet paper concludes “LIVE-AIR showed that lenzilumab treatment of hospitalised patients with COVID-19 can improve the likelihood of survival without the need for mechanical ventilation, with a safety profile similar to that of placebo.”2
“Publication of LIVE-AIR results in this peer-reviewed medical journal is a major achievement. Our goal was to demonstrate that lenzilumab, a variant-agnostic therapy, could address the unmet need in treatment of COVID-19 patients by reducing death or mechanical ventilation. The results describe the positive impact lenzilumab has on improving survival without the need for invasive mechanical ventilation in COVID-19 patients upon hospitalization,” said Cameron Durrant, Chairman and CEO, Humanigen. “As the paper describes ‘60% of LIVE-AIR patients were on room air or low-flow oxygen support. … (Raising) the possibility that lenzilumab might be positioned for use before ICU admission and progression of respiratory failure requiring high-flow oxygen and non-invasive or invasive ventilation.’”2
“This study of the treatment to prevent hyperinflammatory immune response that occurs in some patients infected with SARS-CoV-2 is important,” said Zelalem Temesgen, M.D., Mayo Clinic infectious disease researcher and principal investigator. “The need is great for more therapies for newly hospitalized patients prior to respiratory failure to reduce mortality or mechanical ventilation.”
Lenzilumab is not authorized, or approved, in any country.
“One of the key components of the detrimental hyperinflammatory response in COVID-19 is granulocyte-macrophage colony-stimulating factor (GM-CSF). ... excessive GM-CSF production can contribute to the dysregulated immune response in severe COVID-19, in which, upstream of IL-1 and IL-6, activated T cells target neutrophils and macrophages. Agents that interfere with its actions have high plausibility for benefit, not just in COVID-19, but in other acute inflammatory conditions,”1 noted the commentary.
The Lancet paper notes differences in CRP levels for LIVE-AIR patients compared to those of clinical trials for another immunomodulator to suggest these “findings might indicate the therapeutic potential of targeting a single upstream cytokine earlier in the disease process, guided by baseline CRP. ... The study contributes to the emerging body of evidence about how CRP concentrations relate to the pathogenesis of COVID-19 and to patient and treatment selection.”2 Related to the value of a CRP-guided approach to treatment of COVID-19 patients, the commentary noted “further study of a CRP-guided approach, possibly targeting patients with lower CRP concentrations, earlier in their disease course, ... could therefore be warranted.”1
For hospitalized patients, “we now know that targeting the dysregulated host response is of greater value than targeting the virus.”1 The high level of uncertainty and concern surrounding the emergence of the Omicron variant highlights the ongoing need for variant-agnostic therapies.
About the LIVE-AIR, Phase 3 Study of Lenzilumab
This study was a randomized, double-blind, placebo-controlled, multi-center Phase 3 trial for the treatment and prevention of serious and potentially fatal outcomes in patients hospitalized with COVID-19 pneumonia. The primary objective was to assess whether lenzilumab, in addition to other treatments, which included dexamethasone (or other steroids) and/or remdesivir, could prevent or alleviate the immune-mediated ‘cytokine storm’ and improve survival without ventilation, or ‘SWOV’ (sometimes referred to as ‘ventilator-free survival’). SWOV is a composite endpoint of time to death and time to invasive mechanical ventilation (IMV) and SWOV is an important clinical endpoint that measures not only mortality, but the morbidity associated with mechanical ventilation. Approximately 94% of patients received dexamethasone (or other steroids), 72% received remdesivir, and 69% received both.
The LIVE-AIR study enrolled 520 patients in 29 sites in the US and Brazil who were at least 18 years of age; experienced blood oxygen saturation (SpO2) of less than or equal to 94%; or required low-flow supplemental oxygen, or high-flow oxygen support, or non-invasive positive pressure ventilation; and were hospitalized but did not require IMV. Following enrollment, subjects were randomized to receive three infusions of either lenzilumab or placebo, with each infusion separated by eight hours over a 24-hour period. The LIVE-AIR study achieved its primary endpoint of survival without ventilation measured through day 28 following treatment (HR: 1.54; 95%CI: 1.02-2.32, p=0.040).
Lenzilumab is a proprietary Humaneered® first-in-class monoclonal antibody that has been proven to neutralize GM-CSF, a cytokine of critical importance in the hyperinflammatory cascade, sometimes referred to as cytokine release syndrome, or cytokine storm, associated with COVID-19 and other indications. Lenzilumab binds to and neutralizes GM-CSF, consequently improving outcomes for patients hospitalized with COVID-19. Humanigen believes that its GM-CSF neutralization has the potential to reduce the hyper-inflammatory cascade known as cytokine release syndrome common to chimeric antigen receptor T-cell (CAR-T) therapy and acute Graft versus Host Disease (aGvHD).
In CAR-T, lenzilumab successfully achieved the pre-specified primary endpoint at the recommended dose in a Phase 1b study with Yescarta® in which the overall response rate was 100% and no patient experienced severe cytokine release syndrome or severe neurotoxicity. Based on these results, Humanigen plans to test lenzilumab in a randomized, multicenter, potentially registrational, Phase 2 study to evaluate its efficacy and safety when combined with other commercially available CD19 CAR-T therapies in non-Hodgkin lymphoma. Lenzilumab will also be tested to assess its ability to prevent and/or treat aGvHD in patients undergoing allogeneic hematopoietic stem cell transplantation.
A study of lenzilumab is also underway for patients with chronic myelomonocytic leukemia (CMML) exhibiting RAS pathway mutations. This study will build on evidence from a Phase 1 study, conducted by Humanigen, that showed RAS mutations are associated with hyper-proliferative features, which may be sensitive to GM-CSF neutralization.
For more information, visit www.humanigen.com and follow Humanigen on LinkedIn, Twitter, and Facebook.
Dec. 02, 2021 2:50 AM ET
By: Mamta Mayani, SA News Editor
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 U.S. Food and Drug Administration (FDA) has approved PreHevbrio™ [Hepatitis B Vaccine (Recombinant)] for the prevention of infection caused by all known subtypes of hepatitis B virus (HBV) in adults age 18 years and older. PreHevbrio contains the S, pre-S2, and pre-S1 HBV surface antigens, and is the only approved 3-antigen HBV vaccine for adults in the U.S.
“As we work to implement the ACIP’s new universal hepatitis B vaccine recommendation for all adults ages 19-59, as voted on in November, we benefit from having more tools, including this newly approved 3-antigen hepatitis B vaccine,” said Chari Cohen, DrPH, MPH, Senior Vice President of the Hepatitis B Foundation. “Having more vaccine options will help us effectively expand vaccine uptake, ensure more people are protected from hepatitis B infection, and reach the 2030 goal of eliminating hepatitis B in the U.S.”
Jeff Baxter, VBI’s President and CEO, commented: “We are proud to announce the approval of PreHevbrio, VBI’s first FDA-approved vaccine. This is a substantial achievement that demonstrates the VBI team’s ability to progress vaccine candidates from the clinic through to approval. This approval, however, is just the first step in our mission to provide broad access to our vaccine and to help strengthen the public health effort to put an end to adult HBV infections. We would like to thank the study participants, clinical site investigators, our employees, and all who contributed to this achievement, and we look forward to working with public health and advocacy organizations as we join the fight against hepatitis B.”
The approval of PreHevbrio was based on the results from two Phase 3 clinical studies, PROTECT and CONSTANT, data from which were published, respectively, in The Lancet Infectious Diseases in May 2021 and The Journal of the American Medical Association Network Open in October 2021. The pivotal studies compared PreHevbrio to Engerix-B, a single-antigen HBV vaccine. Data from the PROTECT study showed that PreHevbrio 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 expects to make PreHevbrio available in the U.S. in the first quarter of 2022, and has partnered with Syneos Health for the past two years to ensure commercial readiness.
Outside of the U.S., VBI continues to support the European Medicines Agency’s (EMA) ongoing review of the marketing authorization application for VBI’s 3-antigen HBV vaccine. VBI expects to complete regulatory submissions to the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) and to Health Canada in 2022.
Conference Call Details
Indication and Use
PreHevbrio is indicated for prevention of infection caused by all known subtypes of hepatitis B virus. PreHevbrio is approved for use in adults 18 years of age and older.
Please see full Prescribing Information.
PreHevbrio is an adult hepatitis B vaccine that contains the three hepatitis B surface antigens of the hepatitis B virus – S, pre-S1, and pre-S2. PreHevbrio is also approved for use and commercially available in Israel under the brand name Sci-B-Vac®.
Dec. 01, 2021 8:03 AM ET
Dec 1, 2021
– Treatment with VX-147 led to a statistically significant, substantial and clinically meaningful mean reduction in proteinuria of 47.6% at 13 weeks compared to baseline and was well tolerated –
– Results provide clinical proof of concept for the first genetically targeted approach to treating kidney disease –
– Vertex to advance VX-147 into pivotal development in Q1 2022 –
– Vertex to hold a conference call on these results today, December 1, at 8:30 am ET –
BOSTON--(BUSINESS WIRE)--Dec. 1, 2021-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that, in a Phase 2 proof-of-concept (POC) study in patients with APOL1-mediated focal segmental glomerulosclerosis (FSGS), VX-147 on top of standard of care achieved a statistically significant, substantial and clinically meaningful mean reduction of 47.6% in the urine protein to creatinine ratio (UPCR) at Week 13 compared to baseline. VX-147 was well tolerated. These results provide the first clinical evidence and POC that an oral small molecule APOL1 inhibitor can decrease proteinuria in patients with APOL1-mediated kidney disease. Based on these results, Vertex plans to advance VX-147 into pivotal development in APOL1-mediated kidney disease, including FSGS, in Q1 2022.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211201005492/en/
About the VX-147 Phase 2 Study
The Phase 2 open-label, single-arm study evaluated the efficacy, safety and pharmacokinetics of VX-147 in patients with APOL1-mediated FSGS. Patients with biopsy-confirmed FSGS, two APOL1 genetic variants, proteinuria defined by at least 0.7 g/g in the UPCR and an estimated glomerular filtration rate (eGFR) of at least 27 mL/min/1.73 m2 were eligible for enrollment in the study. Patients were on a stable standard-of-care regimen, which could include an angiotensin-converting enzyme (ACE) inhibitor, an angiotensin II receptor blocker (ARB), immunosuppressants and/or low doses of corticosteroids. Patients were treated with VX-147 for a total of 13 weeks. The primary endpoint was percent change from baseline in UPCR at Week 13. The secondary endpoints were safety and pharmacokinetics. In addition, there is a 28-day safety follow-up period after the last dose of treatment and an optional off-treatment follow-up period of up to 12 weeks after the last dose of treatment. The study is ongoing for these follow-up periods.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211201005492/en/
Source: Vertex Pharmaceuticals Incorporated
Dec. 01, 2021 8:08 AM ET
Applications supported by positive results from the pivotal Phase 3 POETYK-PSO clinical trial program demonstrating superior efficacy of deucravacitinib over Otezla® (apremilast) and placebo in treating adults with moderate to severe plaque psoriasis
U.S. Food and Drug Administration assigned a target action date of September 10, 2022; European Medicines Agency validation confirms the submission is complete and begins the centralized review process
Deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor, would be the first TYK2 inhibitor approved for the treatment of any disease
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) and the European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) goal date of September 10, 2022. These latest regulatory milestones are in addition to the NDA acceptance by Japan's Ministry of Health, Labour and Welfare for deucravacitinib for the treatment of adults with moderate to severe plaque psoriasis, pustular psoriasis and erythrodermic psoriasis.
“There is a strong need for more effective and well-tolerated oral therapies for people living with moderate to severe plaque psoriasis, as many remain undertreated or even untreated,” said Jonathan Sadeh, M.D., MSc., senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “Findings from the pivotal POETYK-PSO trials demonstrate the potential of deucravacitinib to elevate the oral standard of care for individuals who are candidates for systemic therapy. We look forward to continuing to work with the FDA and EMA with the goal of bringing deucravacitinib to patients and physicians as quickly as possible.”
The regulatory applications are based on positive results from the pivotal POETYK PSO-1 and POETYK PSO-2 trials, which evaluated once daily deucravacitinib in patients with moderate to severe plaque psoriasis versus placebo and Otezla® (apremilast). Deucravacitinib demonstrated significant and clinically meaningful improvements in skin clearance, symptom burden and quality of life measures compared to placebo and Otezla. Deucravacitinib was well-tolerated with a low rate of discontinuation due to adverse events, with no clinically meaningful lab abnormalities. Primary results were presented at the American Academy of Dermatology Virtual Meeting Experience in April 2021, and additional analyses were presented at the European Academy of Dermatology and Venereology 30th Anniversary Congress in September 2021.
Bristol Myers Squibb thanks the patients and investigators involved in the POETYK-PSO clinical trial program.
Deucravacitinib (pronounced doo-krav-a-sih-ti-nib) is a first-in-class, oral, selective tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action and is the first and only selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting signaling of interleukin (IL)-23, IL-12 and Type 1 interferon (IFN), key cytokines involved in the pathogenesis of multiple immune-mediated diseases. Deucravacitinib achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Deucravacitinib selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, deucravacitinib does not inhibit JAK1, JAK2 or JAK3.
Deucravacitinib is being studied in multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus and inflammatory bowel disease. In addition to POETYK PSO-1 and POETYK PSO-2, Bristol Myers Squibb is evaluating deucravacitinib in three other Phase 3 studies in psoriasis: POETYK PSO-3 (NCT04167462); POETYK PSO-4 (NCT03924427); POETYK PSO-LTE (NCT04036435). Deucravacitinib is not approved for use in any country.
About the Phase 3 POETYK PSO-1 and POETYK PSO-2 Studies
PrOgram to Evaluate the efficacy and safety of deucravacitinib, a selective TYK2 inhibitor (POETYK) PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) are global Phase 3 studies designed to evaluate the safety and efficacy of deucravacitinib compared to placebo and Otezla® (apremilast) in patients with moderate to severe plaque psoriasis. Both POETYK PSO-1, which enrolled 666 patients, and POETYK PSO-2, which enrolled 1,020 patients, were multi-center, randomized, double-blind trials that evaluated deucravacitinib (6 mg once daily) compared with placebo and Otezla (30 mg twice daily). POETYK PSO-2 included a randomized withdrawal and retreatment period after Week 24.
The co-primary endpoints of both POETYK PSO-1 and POETYK PSO-2 were the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 75 response and those who achieved static Physician's Global Assessment (sPGA) score of 0 or 1 at Week 16 versus placebo. Key secondary endpoints of the trials included the percentage of patients who achieved PASI 75 and sPGA 0/1 compared to Otezla at Week 16 and other measures evaluating deucravacitinib versus placebo and Otezla.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211129005192/en/
Source: Bristol Myers Squibb
GOTHENBURG, Sweden, November 23, 2021 – Isofol Medical AB (http://isofol.se/en/) (publ) (Nasdaq Stockholm: ISOFOL), announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) for the development of the Company’s lead drug candidate arfolitixorin, the stabilized and biologically active pure form of folate ([6R]-MTHF), for treatment of patients with metastatic colorectal cancer (mCRC). The FDA’s decision is based on the potential for arfolitixorin to address a large unmet medical need for new and more effective treatments of mCRC, the second deadliest and third most common form of cancer. Fast Track Designation facilitates frequent communication with the FDA and can result in expedited review timelines and a potential earlier market authorization and approval to ensure that new treatments can be made available quicker for patients with serious diseases.
– We are thrilled that the FDA has granted Fast Track Designation to our lead candidate arfolitixorin. This serves as a strong external validation of arfolitixorin’s potential to benefit patients with this devastating disease. Our next clinical milestone is reaching 300 progression-free survival events in the Phase III AGENT study which means that data can be deblinded so that we can analyze and present top-line results in the first half of 2022. The Fast Track Designation will enable us to engage more frequently with the FDA to optimally plan for the continued development of arfolitixorin and potentially make it the first novel drug to improve the standard of care in mCRC in over 40 years, said Ulf Jungnelius, CEO of Isofol.
As defined by the FDA, Fast Track Designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions, thereby meeting an unmet medical need. The designation allows for such options as eligibility for priority review, if relevant criteria are met, more frequent meetings with FDA, and rolling review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by FDA, rather than waiting until every section of the application is completed before the entire application can be reviewed. The NDA review otherwise usually does not begin until the drug company has submitted the entire application to the FDA. More information about the Fast Track Designation can be found here.
As the first and only pure form of the folate ([6R]-MTHF) that increases 5FU-cytotoxicity, arfolitixorin is currently being evaluated in the global pivotal Phase III AGENT study. The AGENT study is fully recruited and approximately 90 clinics in the United States, Canada, Europe, Australia and Japan have been involved in the study. Isofol’s ambition is to conclude the AGENT study in 2022 and thereafter apply for market approval with the FDA and EMA, which could result in a potential commercialization of arfolitixorin as early as 2023.
Arfolitixorin is Isofol’s proprietary drug candidate being developed to increase the efficacy of standard of care chemotherapy for advanced colorectal cancer. The drug candidate is currently being studied in a global pivotal Phase III study, AGENT. As the key active metabolite of the widely used folate-based drugs, arfolitixorin can potentially benefit all patients with advanced colorectal cancer, as it does not require complicated metabolic activation to become effective.
The Phase III AGENT study is a randomized, controlled, multi-centre study assessing the efficacy and safety of arfolitixorin, [6R]-5,10-methylene-THF acid (MTHF), compared to leucovorin, both used in combination with 5-FU, oxaliplatin, and bevacizumab, in first line metastatic colorectal cancer patients. Patients are randomized in a 1:1 ratio and the primary endpoint is overall response rate (ORR). The key secondary endpoints are progression free survival (PFS) and duration of response (DOR). Other secondary endpoints include overall survival (OS), number of curative metastasis resections, safety, and patient reported outcomes such as quality of life (QoL). Exploratory endpoints include pharmacokinetic (PK) measurements and level of gene expression of folate relevant genes in tumour cells. The study is designed to show superiority for arfolitixorin over leucovorin.
The study has involved approximately 90 clinics in the U.S., Canada, Europe, Australia and Japan. In December 2020, the last of the AGENT study’s 440 patients were recruited, which is the basis in the statistical analysis plan. Isofol is now focusing on completing the ongoing AGENT study where the patients receive first-line standard treatment with either leucovorin or arfolitixorin for metastatic colorectal cancer (mCRC). The company expects that top-line results of the AGENT study will be available during H1 2022. Further information about the study, including patient eligibility requirements, is available at www.clinicaltrials.gov id:NCT03750786.
Nov. 23, 2021 1:55 PM ET
By: Dulan Lokuwithana, SA News Editor
Isofol Medical has received the Fast Track Designation from the FDA for its lead asset, arfolitixorin, in the treatment of metastatic colorectal cancer ((mCRC)), the company said on Tuesday.
Nov. 22, 2021 4:30 PM ET
By: Jonathan M Block, SA News Editor
Nov 22, 2021 7:00 AM
Expanding portfolio with first internally discovered asset in Inflammation and Immunology with internally discovered asset
A highly selective, allosteric TYK2 inhibitor that has shown potent inhibition against pro-inflammatory cytokines in preclinical studies
CAMBRIDGE, Mass. & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines, today announced that the first patient has been dosed in a Phase 1 clinical trial of BGB-23339, a potent, allosteric investigational tyrosine kinase 2 (TYK2) inhibitor internally developed by BeiGene scientists.
TYK2 is a member of the JAK family and functions as a critical mediator in cytokine signaling pathways implicated in multiple immune-mediated disorders, such as psoriasis and inflammatory bowel disease. BGB-23339 is a potent, highly selective, investigational TYK2 inhibitor targeting the regulatory pseudokinase (JH2) domain.
“Discovered and developed by BeiGene, BGB-23339 is a highly selective, potent, allosteric TYK2 inhibitor that has shown promising activity in preclinical evaluation,” commented Lai Wang, Ph.D., Global Head of R&D at BeiGene. “Building on our proven track record in oncology, BeiGene is expanding its clinical focus to discover new modalities and platforms in areas of high unmet need, including inflammation and immunology, to bring innovative, impactful medicines to patients.”
The first-in-human Phase 1 trial (NCT05093270) is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of BGB-23339. The trial is expected to enroll up to 115 healthy volunteers in Australia and/or China.
In addition to its broad portfolio focused on hematological malignancies and solid tumors, BeiGene is applying its research excellence and clinical expertise to address inflammation and immunology, an area of high unmet medical need. BeiGene’s internally developed, highly selective next-generation BTK inhibitor BRUKINSA® (zanubrutinib) is currently being evaluated in a Phase 2 trial in patients with active proliferative lupus nephritis.
BGB-23339 is a potent, highly selective, allosteric, investigational tyrosine kinase 2 (TYK2) inhibitor discovered and being developed by BeiGene. TYK2 is a member of the JAK family and functions as a critical mediator in cytokine signaling pathways implicated in multiple immune-mediated disorders. Designed to target the regulatory pseudokinase (JH2) domain on TYK2, BGB-23339 has demonstrated strong selectivity in preclinical studies with potent inhibition of interleukin (IL)-12, IL-23, and Type 1 interferons (IFNs)—pro-inflammatory cytokines that play a determinant role in the induction of inflammation. BGB-23339 is currently being evaluated in a Phase 1 clinical study.
To learn more about BeiGene, please visit www.beigene.com
View source version on businesswire.com: https://www.businesswire.com/news/home/20211122005809/en/
Nov. 22, 2021 9:06 AM ET
By: Mamta Mayani, SA News Editor
Innovent Releases the ORIENT-31 Phase 3 Study First Interim Analysis Results of Sintilimab plus BYVASDA® (bevacizumab biosimilar injection) and Chemotherapy in Patients with EGFR-mutated Nonsquamous Non-small Cell Lung Cancer who Progressed After EGFR-TKIPublished on: Nov 22nd, 2021Back
SAN FRANCISCO, U.S. and SUZHOU, China, November 22, 2021 — Innovent Biologics, Inc. (“Innovent”) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, today announced first interim analysis results of the randomized, double-blinded, multi-center Phase 3 ORIENT-31 study conducted in China evaluating sintilimab and anti-VEGF antibody combination therapy (i.e., sintilimab plus BYVASDA® [bevacizumab biosimilar injection] combined with chemotherapy [pemetrexed and cisplatin]) in patients with EGFR-mutated non-squamous non-small cell lung-cancer (nsqNSCLC) who progressed after EGFR-TKI therapy in an oral presentation at the ESMO (European Society for Medical Oncology) Virtual Plenary: November 2021 (Abstract #300).
In the first interim analysis reviewed by the Independent Data Monitoring Committee (IDMC), in the intent-to-treat (ITT) population, based on assessment by the Independent Radiographic Review Committee (IRRC), Arm A (sintilimab plus BYVASDA®[bevacizumab biosimilar injection] in combination with chemotherapy group) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with Arm C (chemotherapy group), with a HR of 0.464 (95%CI: 0.337, 0.639; p<0.0001). The median progression-free survival (PFS) (95%CI) was 6.9 months (6.0, 9.3) in Arm A, and 4.3 months (4.1, 5.4) in Arm C. The prespecified PFS futility analysis that compares Arm A to Arm B (sintilimab and chemotherapy group) did not cross futility stopping boundary (HR=0.726, 95%CI: 0.528, 0.998). A numerical benefit of adding BYVASDA® (bevacizumab biosimilar injection) to sintilimab and chemotherapy combination was observed (based on IRRC assessment). Additionally, the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were improved in Arm A compared with Arm C, and the results of PFS, ORR and DOR assessed by the investigator were consistent with the results assessed by IRRC. The PFS data of Arm B vs Arm C was immature yet, with a numerical benefit observed as well. The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and BYVASDA® (bevacizumab biosimilar injection), without new unexpected safety signals. Innovent plans to review these results and file the supplemental New Drug Application (sNDA) to the National Medical Products Administration (NMPA) in China in the near future.
The principal investigator of the ORIENT-31, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, “Despite initial clinical response to EGFR-TKI, virtually all advanced EGFR-mutated NSCLC inevitably acquire resistance mechanisms and progress after treatment with an EGFR-TKI. For those patients with EGFR-mutated advanced nsqNSCLC who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is the current standard of care, but with limited benefit. New treatment options are imperative for this unmet medical need. Globally, ORIENT-31 is the first prospective, double-blind Phase 3 study to demonstrate significant PFS benefit of combination therapy of PD-1 and VEGF inhibitors with chemotherapy compared to standard care of therapy in this patient population. The study has shown the clinical value of adding sintilimab plus BYVASDA® (bevacizumab biosimilar injection) to platinum-based chemotherapy. I am honored to have this opportunity to share the results of this study as an oral presentation at this year's ESMO Virtual Plenary. This modified regimen brings forth a new and more effective treatment option and provides clinically meaningful benefits to patients with EGFR-mutated nsqNSCLC following treatment with an EGFR TKI.”
Dr. Hui Zhou, Senior Vice President of Innovent, stated, “Lung cancer is one of the most prevalent cancers and remains the leading cause of cancer-related mortality both in China and worldwide. EGFR-mutated NSCLC is the most prevalent molecular subtype in Chinese lung cancer patients, accounting for 40% to 50% of nsqNSCLC. While immunotherapy has greatly changed the treatment paradigm for many malignancies, it has not yet conquered driver genes mutated cancers. Drug resistance is unavoidable for patients with EGFR-mutated advanced NSCLC after first, second and third generation EGFR-TKIs treatments, with limited treatment options, representing a large unmet medical need. The ORIENT-31 data at this year’s ESMO indicates the potential of combination therapy to prolong lives of these patients. We are grateful for all the contributions made by the investigators and patients in the ORIENT-31 study – together we accomplished this meaningful milestone.”
About the ORIENT-31 Study
ORIENT-31 is a randomized, double-blind, multi-center Phase 3 clinical study conducted in China evaluating sintilimab, with or without BYVASDA® (bevacizumab biosimilar injection), combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic nsqNSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT003802240). The primary endpoint is PFS as assessed by BIRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, ORR and safety.
Eligible patients included: patients with disease progression following first or second generation EGFR TKI and confirmed as T790M negative, or T790M positive but further progressed on third generation EGFR-TKI treatment, or patients with disease progression following third generation EGFR TKI as first line treatment.
Patients were randomized in a 1:1:1 ratio to receive sintilimab plus BYVASDA® (bevacizumab biosimilar injection) combined with pemetrexed and cisplatin (Arm A), sintilimab plus placebo 2 combined with pemetrexed and cisplatin (Arm B), or placebo 1 plus placebo 2 combined with pemetrexed and cisplatin (Arm C). After 4 cycles of combination treatment, patients will receive maintenance treatment of sintilimab plus BYVASDA® and pemetrexed, sintilimab plus placebo 2 and pemetrexed, placebo 1 plus placebo 2 and pemetrexed, until radiographic disease progression, unacceptable toxicity or any other conditions that required treatment discontinuation. Target accrual is 480 patients. By the data cutoff date of the first interim analysis, 444 patients were enrolled.
Sintilimab, marketed as TYVYT® (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab worldwide, to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.
In China, sintilimab has been approved for four indications, including:
Additionally, Innovent currently has two regulatory submissions accepted for review in China for sintilimab monotherapy for the first-line treatment of esophageal squamous cell carcinoma, and for sintilimab in combination with chemotherapy for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Additionally, three clinical studies of sintilimab have met their primary endpoints:
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.
Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.
For more information, please visit: www.innoventbio.com.
Nov. 22, 2021 12:54 AM ET
By: Mamta Mayani, SA News Editor
INNOVENT BIOLOGICS, INC. (1801)
November 22, 2021 at 7:00 AM EST
ROCKVILLE, Md., Nov. 22, 2021 /PRNewswire/ --
REGENXBIO Inc. (Nasdaq: RGNX) today announced the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for RGX-202, a potential one-time gene therapy for the treatment of Duchenne muscular dystrophy (Duchenne). RGX-202 is designed to deliver a novel, optimized microdystrophin transgene with a unique C-terminal domain and a muscle specific promoter to support targeted therapy for improved resistance to muscle damage associated with Duchenne. RGX-202 uses REGENXBIO's proprietary NAV® AAV8 vector.
"This important designation is a milestone in the development of RGX-202 and highlights the need for potential new treatment options for patients with Duchenne," said Olivier Danos, Ph.D., Chief Scientific Officer of REGENXBIO. "The novel microdystrophin transgene in RGX-202 includes coding regions that retain essential functional elements of naturally occurring dystrophin to potentially improve muscle strength and resistance in patients with Duchenne. We look forward to advancing this one-time gene therapy into the clinic."
REGENXBIO expects to submit an Investigational New Drug (IND) application to the FDA for RGX-202 by the end of 2021. Commercial-scale cGMP material has already been produced at 1,000 liter capacity using REGENXBIO's suspension cell culture manufacturing process, and the Company's internal cGMP facility is expected to allow for production up to 2,000 liters for the clinical development of RGX-202.
FDA Orphan Drug Designation is granted to investigational therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug status provides benefits to drug developers, including assistance in the drug development process, tax credits for clinical costs, exemptions from certain FDA fees and seven years of post-approval marketing exclusivity.
RGX-202 is designed to deliver a novel microdystrophin transgene which retains key elements of the dystrophin protein, including an extended coding region of the C-Terminal (CT) domain found in naturally-occurring dystrophin, as well as other fundamental improvements to the transgene. Presence of the CT domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle targeting promoter (Spc5-12).
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SOURCE REGENXBIO Inc.
Nov. 22, 2021 8:05 AM ET
By: Jonathan M Block, SA News Editor
November 22, 2021
FDA Accepts NDA for Linzagolix for the Management of Heavy Menstrual Bleeding Associated with Uterine Fibroids
Ad hoc announcement pursuant to Art. 53 LR of the SIX Swiss Exchange
GENEVA, Switzerland November 22, 2021 – Obseva SA (NASDAQ: OBSV; SIX: OBSN), a biopharmaceutical company developing and commercializing novel therapies to improve women’s reproductive health,today announced that the New Drug Application (NDA) for linzagolix for the management of heavy menstrual bleeding associated with uterine fibroids in premenopausal women has been accepted for review by the United States Food and Drug Administration (FDA). The submission is based on data from the two Phase 3 PRIMROSE trials. Linzagolix has a differentiated profile and if approved, would be the first and only GnRH receptor antagonist with flexible dosing options for uterine fibroids, including a low dose option to address the needs of women who cannot or do not want to take hormones.1,4 The FDA set a target action date of September 13, 2022 for this NDA under the Prescription Drug User Fee Act (PDUFA).
“Today marks an important milestone not only in the linzagolix clinical development process, but for Obseva as a company, and most importantly, the millions of women living with uterine fibroids throughout the US. Linzagolix is a significant innovation in the field of women’s health – an area that is consistently underinvested in – and we are incredibly excited about the potential of bringing this important treatment to market” said Brian O’Callaghan, CEO of Obseva. “We are encouraged by our positive Phase 3 PRIMROSE results. If approved, we believe linzagolix will address a significant unmet need in offering a more individualized treatment option for a broader range of women.”
The Phase 3 PRIMROSE trials of linzagolix (PRIMROSE 1: US; n=574 and PRIMROSE 2: Europe and US; n=535) investigated the efficacy and safety of two dosing regimens, 100mg once daily and 200mg once daily, alone or in combination with hormonal ABT (1 mg estradiol and 0.5 mg norethisterone acetate) for the treatment of heavy menstrual bleeding associated with uterine fibroids. The NDA submission comprises positive 24-week treatment results from both studies, as well as supportive results from Week 52 and the 76-week post-treatment follow-up.
“Uterine fibroids can have a devastating impact on women’s day-to-day life. With its unique dosing options, linzagolix has the potential to significantly advance medical options for women,” stated Elizabeth Garner, MD, MPH, Chief Medical Officer of Obseva. “A dosing option without hormonal ABT would be welcomed by the significant number of women who either have contraindications to or a personal preference to avoid the use of estrogen-based therapies, while also providing a dosing option for women in whom hormonal ABT is indicated.”
The linzagolix marketing authorization application (MAA) was validated by the European Medicine Agency (EMA) with an approval recommendation from the Committee for Medicinal Products for Human Use (CHMP) expected in Q4 2021. Obseva announced previously that the company has entered into a partnership with Syneos Health to support commercialization of linzagolix in the US and EU.
Linzagolix is a novel, once daily, oral GnRH receptor antagonist with a potentially best-in-class profile1,2,3. Linzagolix is the subject of submitted marketing authorization applications for the treatment of heavy menstrual bleeding associated with uterine fibroids and is currently in late-stage clinical development for the treatment of pain associated with endometriosis. Obseva licensed linzagolix from Kissei in late 2015 and retains worldwide commercial rights, excluding Asia, for the product. Linzagolix is not currently approved anywhere in the world.
About the Phase 3 PRIMROSE Program in Uterine Fibroids
PRIMROSE 1 & 2 were prospective, randomized, parallel group, double-blind, placebo-controlled Phase 3 studies that investigated the efficacy and safety of two dosing regimens of linzagolix, 100 mg and 200 mg once daily, alone and in combination with hormonal ABT (1 mg estradiol and 0.5 mg norethisterone acetate) for the treatment of heavy menstrual bleeding associated with uterine fibroids. PRIMROSE 1 was conducted in the United States and enrolled 574 women. PRIMROSE 2 was conducted in Europe and the United States and enrolled 535 women. Both trials comprised a 52-week treatment period followed by a 6-month post treatment follow-up period. Additional information can be found here.
For more information, please visit www.ObsEva.com.
Nov. 22, 2021 1:26 AM ET ObsEva SA (OBSV)
By: Mamta Mayani, SA News Editor
bluebird bio Announces FDA Priority Review of Biologics License Application for beti-cel Gene Therapy for Patients with β-thalassemia Who Require Regular Red Blood Cell Transfusions
If approved, beti-cel will be the first one-time treatment option to address the underlying genetic cause of disease
Current standard of care relies on regular red blood cell transfusions and iron management that carry the risk of progressive multi-organ damage and increased risk of morbidity and mortality
FDA set PDUFA date of May 20, 2022
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 22, 2021-- bluebird bio, Inc. (Nasdaq: BLUE) today announced that the U.S. Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for betibeglogene autotemcel (beti-cel) for priority review. Beti-cel is a potentially transformative gene therapy for adult, adolescent and pediatric patients with β-thalassemia across all genotypes who require regular red blood cell (RBC) transfusions. If approved, beti-cel will be the first one-time treatment that addresses the underlying genetic cause of disease for patients living with β-thalassemia in the U.S.—offering an alternative to regular RBC transfusions and iron chelation therapy. The agency has set a Prescription Drug User Fee Act (PDUFA) goal date of May 20, 2022.
“The FDA’s acceptance of our BLA for beti-cel brings us one step closer to potentially providing a one-time treatment that can address the underlying cause of β-thalassemia and offer patients freedom from regular transfusions,” said Andrew Obenshain, chief executive officer, bluebird bio. “It’s also a critical milestone for bluebird bio as an independent severe genetic disease company. We are moving forward with great discipline and exceptional care to deliver on our commitments to patients and achieve our near-term goal of launching three first-in-class gene therapies in the U.S.”
The BLA for beti-cel is based on data from bluebird bio’s Phase 3 studies HGB-207 (Northstar-2) and HGB-212 (Northstar-3), the Phase 1/2 HGB-204 (Northstar) and HGB-205 studies, and the long-term follow-up study LTF-303. Together, these studies represent more than 220 patient-years of experience with beti-cel. As of March 9, 2021, the results include a total of 63 pediatric, adolescent and adult patients, including long-term efficacy and safety results in two patients with more than seven years follow-up. Additional data through August 2021 will be presented at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 11-14, 2021.
About betibeglogene autotemcel (beti-cel)
betibeglogene autotemcel (beti-cel) (pronounced BEH tee cell) is a one-time gene therapy custom-designed to treat the underlying cause of β-thalassemia in patients who require regular red blood cell (RBC) transfusions. Beti-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs) in order to correct the deficiency of adult hemoglobin that is the hallmark of β-thalassemia. Once a patient has the βA-T87Q-globin gene, they have the potential to produce beti-cel-derived adult hemoglobin (HbAT87Q) at levels that may eliminate the need for transfusions. In Phase 3 beti-cel studies, 89% (32/36) of evaluable patients across all ages and genotypes, including pediatric patients as young as four years of age and those with the most severe (β0/β0) genotypes, achieved transfusion independence, which is defined as no longer needing RBC transfusions for at least 12 months while maintaining a weighted average Hb of at least 9 g/dL.
beti-cel is manufactured using the BB305 lentiviral vector (LVV), a third-generation, self-inactivating LVV that has been studied for more than a decade across multiple therapeutic areas.
Adverse reactions considered related to beti-cel were uncommon and consisted primarily of non-serious infusion-related reactions that occurred on the day of infusion (e.g. abdominal pain, hot flush, dyspnea, tachycardia and non-cardiac chest pain) and cytopenias (e.g. thrombocytopenia, leukopenia and neutropenia). Pain in extremity shortly after treatment was also documented. One of these adverse events (AE) was a serious adverse event (SAE) of thrombocytopenia considered possibly related to beti-cel and has resolved.
The majority of AEs and SAEs in the beti-cel clinical development program were unrelated to beti-cel and consistent with the known side effects of HSC collection and busulfan conditioning regimen (including several SAEs of veno-occlusive disease that resolved with treatment).
The Phase 3 Northstar-2 (HGB-207) and Northstar-3 (HGB-212) studies evaluating beti-cel are ongoing; enrollment is complete, and all patients have been treated. bluebird bio is also conducting a long-term follow-up study, LTF-303, to monitor safety and efficacy for people who have participated in bluebird bio-sponsored beti-cel clinical studies through 15 years post-treatment.
bluebird bio is a trademark of bluebird bio, Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211122005845/en/
Source: bluebird bio, Inc.
Nov. 22, 2021 6:45 AM ET
By: Mamta Mayani, SA News Editor
CRISPR Therapeutics Announces FDA Regenerative Medicine Advanced Therapy (RMAT) Designation Granted to CTX110™ for the Treatment of Relapsed or Refractory CD19+ B-cell malignancies
ZUG, Switzerland and CAMBRIDGE, Mass., Nov. 22, 2021 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX110™, its wholly-owned allogeneic CAR-T cell therapy targeting CD19+ B-cell malignancies.
“This RMAT designation is based on the encouraging clinical data we have presented thus far, and it is an important milestone that recognizes the transformative potential of CTX110 for the treatment of hematological malignancies,” said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. “We look forward to working closely with the FDA as we continue our efforts to bring this important new therapeutic modality to patients.”
Established under the 21st Century Cures Act, RMAT designation is a dedicated program designed to expedite the drug development and review processes for promising pipeline products, including genetic therapies. A regenerative medicine therapy is eligible for RMAT designation if it is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug or therapy has the potential to address unmet medical needs for such disease or condition. Similar to Breakthrough Therapy designation, RMAT designation provides the benefits of intensive FDA guidance on efficient drug development, including the ability for early interactions with FDA to discuss surrogate or intermediate endpoints, potential ways to support accelerated approval and satisfy post-approval requirements, potential priority review of the biologics license application (BLA) and other opportunities to expedite development and review.
CTX110, a wholly owned program of CRISPR Therapeutics, is a healthy donor-derived gene-edited allogeneic CAR-T investigational therapy targeting Cluster of Differentiation 19, or CD19. CTX110 is being investigated in the ongoing CARBON trial.
The ongoing Phase 1 single-arm, multi-center, open label clinical trial, CARBON, is designed to assess the safety and efficacy of several dose levels of CTX110 for the treatment of relapsed or refractory B-cell malignancies.
For more information, please visit www.crisprtx.com.
CRISPR THERAPEUTICS® standard character mark and design logo and CTX110™ are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
Nov. 22, 2021 9:44 AM ET
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