CCR8 is a chemokine receptor that is enriched on immunosuppressive tumor-infiltrating T regulatory (TITR) cells, and GS-1811 has the potential to be the first drug in the class to reach the market, according to Gilead. Increased CCR8 expression in tumors has been linked to a poor prognosis in several types of cancer, including lung cancer, in humans.
Gilead licensed the drug as part of a flurry of immuno-oncology deals that also included Arcus’ zimberelimab, a stake in Tizona Therapeutics, and a broad alliance with Tango Therapeutics. The buyout provides Jounce with much-needed cash as it deals with recent disappointing clinical data with its lead drug candidate, ICOS agonist vopratelimab, whose future is now in doubt. Vopratelimab in combination with the PD-1 inhibitor pimivalimab failed to outperform pimivalimab alone in the phase II SELECT trial earlier this year, and it also failed to outperform pimivalimab alone in the EMERGE trial in 2020 in combination with BMS’ CTLA4 inhibitor Yervoy (ipilimumab).
FDA Places Clinical Hold on Biogen’s Multiple Sclerosis Drug
Biogen’s efforts to replenish its multiple sclerosis pipeline have been hampered after the FDA imposed a clinical hold on a drug candidate licensed from China’s InnoCare last year for USD 125 million upfront. The US Food and Drug Administration has placed the oral BTK inhibitor orelabrutinib on partial clinical hold, which means that new patients cannot be enrolled in clinical trials, and patients who have been on the drug for 70 days or less must discontinue treatment.
Those who have been taking orelabrutinib for at least 70 days can continue to do so. The drug is currently in a phase II trial in relapsing-remitting multiple sclerosis (RRMS), as well as early-stage studies in other autoimmune diseases. According to InnoCare, the restrictions will also apply to studies currently underway outside of the United States. The decision was motivated by a “limited number” of drug-induced liver injury cases observed in orelabrutinib trials. According to the study, the cases were reversible after the drug was stopped being administered, and the phase II Multiple Sclerosis trial is nearly complete.
Liver injuries also prompted the FDA to impose a partial clinical hold on Sanofi’s BTK inhibitor tolebrutinib (SAR442168) earlier this year, stalling a program that was a key component of the company’s USD 3.7 billion acquisition of Principia Biopharma.
Orelabrutinib is already approved in China as a second-line therapy for two types of blood cancer: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). Biogen licensed rights to InnoCare’s drug in a deal worth up to USD 840 million after feeling the pinch with its current Multiple Sclerosis drugs such as Tecfidera (dimethyl fumarate), Avonex (interferon beta-1a), and Tysabri (natalizumab).
Pfizer Announces Positive Top-Line Results from Phase 3 Study of Hemophilia B Gene Therapy Candidate
Pfizer Inc. (NYSE: PFE) announced positive top-line results from the Phase 3 BENEGENE-2 study (NCT03861273) evaluating fidanacogene elaparvovec, an investigational gene therapy for the treatment of adult males with moderately severe to severe hemophilia B.
Fidanacogene elaparvovec is a novel, investigational gene therapy that contains a bio-engineered AAV capsid and a high-activity human coagulation FIX gene. Once treated with Fidanacogene neparvovec, individuals with haemophilia B should be able to create FIX on their own, rather than needing to receive exogenous FIX. The BENEGENE-2 study met its primary endpoint of non-inferiority and superiority in the annualized bleeding rate (ABR) of total bleeds post-fidanacogene elaparvovec infusion versus prophylaxis regimen with Factor IX (FIX), administered as part of usual care. As per the updates from Pfizer, the key secondary endpoints showed a 78% reduction in treated ABR (p=0.0001) and a 92% reduction in annualized infusion rate (p<0.0001). Through the Phase 1/2 trials, the Fidanacogene elaparvovec was generally well-tolerated, with a safety profile.
Pfizer licensed SPK-9001 (fidanacogene elaparvovec), from Spark Therapeutics pursuant to a December 2014 agreement. As per the deal, Spark Therapeutics was responsible for conducting all Phase 1/2 studies for the investigational gene therapy, while Pfizer to look for the pivotal studies and regulatory activities. Moreover, Pfizer looks after the potential global commercialization.
Hemophilia, a rare genetic bleeding disorder that causes the blood to take a long time to clot. People with hemophilia B have a deficiency in clotting FIX, a specific protein in the blood. As per the estimate, in 2021, more than 38,000 people worldwide were living with hemophilia B in 2021. As per DelveInsight, the total prevalent population of Hemophilia B in the 7MM in 2020 was 10,739 and is expected to rise by 2032. Earlier in November 2022, the US Food and Drug Administration (FDA) approved the first gene therapy for the genetic blood-clotting disorder hemophilia B with a one-time treatment that costs US$3.5 million. The approval and the launch of Pfizer’s fidanacogene elaparvovec is anticipated to further intensify the hemophilia B therapeutics market with an alternative option for patients suffering from this rare indication.
MediWound Announces FDA Approval of NexoBrid® for the Treatment of Severe Thermal Burns in Adults
On December 29, 2022, MediWound Ltd. (Nasdaq: MDWD) announced that the U.S. Food and Drug Administration (FDA) has approved NexoBrid® (anacaulase-bcdb) for the removal of eschar in adults with deep partial-thickness and/or full-thickness thermal burns.
NexoBrid (anacaulase-bcdb) is a botanical drug product containing proteolytic enzymes indicated for the removal of eschar in adults with deep partial- and/or full-thickness thermal burns. The BLA submission leading to FDA approval covered by a comprehensive battery of pre-clinical studies and eight clinical studies, including the pivotal Phase 3 U.S. clinical study (DETECT), which evaluated the efficacy and safety of NexoBrid in adult patients with deep partial-thickness and full-thickness thermal burns of 3%-30% of total body surface area (TBSA).
The study met its primary endpoint of incidence of ≥95% eschar removal compared to gel vehicle, as well as all secondary endpoints, including shorter time to eschar removal, lower incidence of surgical eschar removal, and lower blood loss compared to surgical and non-surgical standard of care (SOC), including both surgical and non-surgical eschar removal methods, with highly statistically significant results.
NexoBrid is already approved for use in 43 countries, including the European Union, Japan, India, and other international markets. Vericel Corporation (Nasdaq: VCEL) holds an exclusive license to commercialize NexoBrid in North America. MediWound will receive a $7.5 million milestone payment from Vericel Corporation, triggered by the FDA approval of NexoBrid.
UCB Announces FDA Acceptance of BLA Resubmission for Bimekizumab
UCB declared that the U.S. Food and Drug Administration has accepted for review the Biologics License Application resubmission for bimekizumab to treat adults with moderate to severe plaque psoriasis. The resubmission was given a “Class 2” designation by the FDA, with a six-month evaluation period. The FDA’s response is anticipated in the second quarter of 2023.
Emmanuel Caeymaex, Executive Vice President of Immunology Solutions and Head of U.S. UCB, said, “the FDA acceptance of our resubmitted application for bimekizumab is positive news that takes us one step closer to providing the first dual IL-17A and IL-17F inhibitor to fulfill the unmet needs of people suffering with moderate to severe plaque psoriasis in the United States. We will continue to work with the FDA throughout the review process to bring bimekizumab to the dermatology community in the United States as soon as possible”.
In November 2022, UCB declared the BLA resubmission for bimekizumab to treat patients suffering from moderate to severe plaque psoriasis after receiving a complete response letter in May 2022.
FDA Approves TG Therapeutics’ Briumvi for Multiple Sclerosis
TG Therapeutics announced the U.S. Food and Drug Administration had approved BRIUMVI for treating relapsing forms of multiple sclerosis, including relapsing-remitting disease, clinically isolated syndrome, and active secondary progressive disease, in adults.
Approval was granted for this disease based on data findings from the ULTIMATE I & II Phase III trials, which showed superiority over teriflunomide in significantly reducing the annualized relapse rate, the number of T1 Gd-enhancing lesions and the number of new or enlarging T2 lesions. Results from the ULTIMATE I & II trials were published in The New England Journal of Medicine in August 2022.BRIUMVI is the first and only anti-CD20 monoclonal antibody given to patients suffering from relapsing multiple sclerosis that can be administered in a one-hour infusion following the starting dose. A 150 mg infusion is given on day one over the course of four hours, a 450 mg infusion is given on day 15, and then 450 mg infusions are given every 24 weeks over the course of an hour.
