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Pictured: Front of FDA headquarters/Grandbrothers/Adobe Stock Friday, AbbVie and Genmab won the FDA’s greenlight for their bi-specific T-cell engager epcoritamab-bysp, now with the brand name Epkinly, for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults. Epkinly was approved under the regulator’s accelerated pathway and is also indicated for DLBCL due to indolent lymphoma and high-grade B-cell lymphoma, after at least two lines of systemic treatment. Epkinly’s label bears a boxed warning for cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both of which can become life-threatening. The DLBCL treatment might also lead to serious or fatal infections, as well as carry a risk of cytopenias and embryo-fetal toxicity. Friday’s approval is based on response rate and durability of response data from the pivotal Phase I/II open-label EPCORE NHL-1 trial. Epkinly treatment led to an overall response rate of 61% and a complete response rate of 38%. The median duration of response was 15.6 months in relapsed or refractory DLBCL patients who had been heavily pretreated. To keep Epkinly on the market, AbbVie and Genmab need to run a confirmatory trial to verify the clinical benefit of their T-cell engager. Epkinly works by binding to both the CD3 protein on T cells and CD20 protein commonly found on B cells. CD20 is a well-validated target in B-cell malignancies. Epkinly exploits this by bridging the malignant B-cells with T-cells, which allow the cancer killers to induce inflammation in the vicinity of the cancer cells and cause its destruction. According to the companies’ press announcement, Epkinly is the first subcutaneous bi-specific antibody for DLBCL. AbbVie and Genmab jointly developed Epkiny under a June 2020 cancer collaboration, which involved a $750 million upfront payment from AbbVie, along with the promise of up to $3.15 billion in potential milestones. Blood Cancer Competition With Friday’s approval, Epkinly edges out Roche’s own bi-specific antibody glofitamab, also being proposed for DLBCL. The FDA accepted glofitamab’s Biologics License Application in January 2023 and granted the therapy its Priority Review designation. The agency is set to release a verdict on July 1. In May 2022, Genentech, the Roche subsidiary responsible for developing glofitamab, announced positive data for the bi-specific engager in aggressive relapsed or refractory DLBCL. In the Phase II NP30179 expansion study, glofitamab had a 39.4% complete response rate, slightly better than Epkinly’s showing in EPCORE NHL-1. Overall response, however, was lower, at 51.6% after glofitamab treatment. However, in the absence of head-to-head trials, direct comparison of response data should be done with caution and cannot be used to draw definitive conclusions about either drug’s efficacy. Both Epkinly and glofitamab are also being assessed for the first-line treatment of DLBCL. In this setting, Roche has a slight edge over AbbVie and Genmab, with the former’s Polivy (polatuzumab vedotin-piiq) winning the FDA’s approval last month as part of a five-drug regimen including Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone. Polivy is now fully approved in first-line DLBCL, following its accelerated approval in June 2019. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Pictured: FDA Action Alert graphic/@Nicole Bean This week, the FDA is set to decide on an investigational gene therapy for a rare skin disease and a bi-specific antibody for cancer. The regulator will also convene advisory committees for two applications. Read below for more. Krystal Awaits Verdict for Gene Therapy for Rare Skin Disease On May 19, the FDA will decide on Krystal Biotech’s investigational gene therapy B-VEC (beremagene geperpavec) for the treatment of dystrophic epidermolysis bullosa (DEB). DEB is a rare and severe skin condition caused by mutations in the COL7A1 gene, which under healthy conditions, produces the type VII collagen (COL7) protein. In turn, COL7 forms part of anchoring fibers that connect the inner and outer layers of the skin. This anchoring function of COL7 is faulty in DEB, which manifests as very fragile skin prone to blistering, tearing and wounding from even light friction. These open wounds eventually lead to severe infections and fibrosis. Patients with DEB are also at an elevated risk of an aggressive type of squamous cell carcinoma. Designed to be administered topically, B-VEC works by delivering two functional copies of the COL7A1 gene to open wounds. It has won the FDA’s Fast Track, Rare Pediatric Disease, Orphan Drug and Regenerative Medicine Advanced Therapy designations. Krystal submitted its BLA for B-VEC in June 2022, backing it with data from two placebo-controlled trials. In the Phase I/II Gem 1/2 study, treatment with B-VEC enhanced the expression of functional COL7, which in turn led to better wound closure. Meanwhile, in the Phase III GEM-3 trial, 67% of patients treated with B-VEC achieved complete wound healing after six months as compared with only 22% of placebo counterparts, achieving the study’s main endpoint. Genmab/AbbVie Seek Approval for Lymphoma Drug AbbVie and its Danish partner Genmab are seeking the FDA’s nod for their investigational bi-specific antibody epcoritamab for the treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL). The FDA is set to decide on the BLA by May 21. In their application, which the FDA accepted in November 2022 and tagged for Priority Review, the pharma partners presented safety and preliminary data from the LBCL cohort of their pivotal EPCORE NHL-1 study, a Phase II open-label clinical trial. Patients treated with epcoritamab saw an overall response rate of 63% and a complete response rate of 39%. The candidate also had a favorable safety pro did not induce grade 4/5 cytokine release syndrome. Most side effects were mild or moderate. Epcoritamab works by binding to the CD3 protein found on T cells and to the CD20 protein, which is commonly expressed on B cells and is a well-validated target in B cell malignancies. If approved, epcoritamab could become the first subcutaneous bi-specific antibody for the treatment of LBCL. AbbVie and Genmab inked their cancer collaboration in June 2020. For an upfront payment of $750 million, AbbVie gained access to Genmab’s next-generation antibody pipeline, which includes epcoritamab. The agreement also entitles Genmab to up to $3.15 billion in potential milestones. Pfizer’s RSV Vaccine Faces Adcomm Again On May 18, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will again convene to discuss Pfizer’s respiratory syncytial virus (RSV) vaccine candidate Abrysvo—this time for its proposed use in infants from birth through 6 months of age. While Pfizer narrowly lost the race to see an RSV vaccine for elderly adults through to the market (GSK secured an FDA approval for its Arexvy on May 3), the New York-based pharma is leading the pack in terms of a pediatric shot. Pfizer is anticipating its approval in the adult setting this month. In February 2023, the FDA accepted Pfizer’s BLA seeking approval for the maternal injection of its RSV vaccine to induce immunity in infants, with a target action date of August 2023. The pharma backed its application with top-line data from the Phase III MATISSE study, which found a 66.7% vaccine efficacy against RSV-associated lower respiratory tract illness (LRTI) with two or more symptoms. Against a more severe presentation including at least three symptoms, Pfizer’s investigational shot had an efficacy rate of 85.7%. In April 2023, Pfizer published more complete data from MATISSE in the New England Journal of Medicine. At 90 and 180 days after birth, the vaccine candidate was 81.8% and 69.4% effective at decreasing medically attended LRTI associated with RSV infections, respectively. Adcomm Convenes for Intercept’s Liver Fibrosis Treatment The FDA will convene a panel of external experts on May 19 regarding Intercept Pharmaceuticals’ obeticholic acid (OCA) 25 mg oral tablets, proposed to treat pre-cirrhotic liver fibrosis arising from non-alcoholic steatohepatitis (NASH). Intercept first submitted an NDA for the 25-mg OCA oral tablets in September 2019, which the FDA rejected in June 2020. The company resubmitted the NDA in December 2022, which the FDA accepted in January 2023. Intercept is seeking accelerated approval. In March 2023, the FDA announced it would hold an advisory committee meeting to discuss the application. Intercept supported its NDA with data from the OCA NASH clinical development program, which includes two interim 18-month data readouts from the Phase III REGENERATE study. Enrolling more than 2,400 patients, REGENERATE is a randomized, double-blinded and placebo-controlled international study evaluating the safety and efficacy of OCA in liver fibrosis due to NASH. Findings from 931 participants at the pre-specified interim analysis showed that the oral medication led to a significant improvement in liver fibrosis by at least one stage without aggravating NASH. The FDA’s target action date is June 22. Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

The Food and Drug Administrations main office for reviewing new medicines cleared 37 in 2022, closing out the year with approvals of treatments for HIV, lymphoma and multiple sclerosis.The total was the lowest number since 2016, when the FDAs Center for Drug Evaluation and Research granted 22 approvals, and was well below last years figure of 50. The center, known as CDER, approves most pharmaceutical treatments, as well as common biologic drugs like monoclonal antibodies.While calendar year totals can fluctuate for many reasons, they are sometimes looked to as a shorthand value of the industrys research and development productivity. Another FDA office, the Center for Biologics Evaluation and Research, is responsible for clearing more complex biologic drugs like vaccines,cell and gene therapies, and approved seven new medicines in 2022.CDERs final decisions of last year included Dec. 22 approvals for Gilead Sciences Sunlenca, for people with drug-resistant HIV, and Roches Lunsumio, for relapsed or refractory lymphoma. The agency approved TG Therapeutics Briumvi for relapsing multiple sclerosis on Dec. 28, as well as a treatment for thermal burns.Sunlenca and Lunsumio, in particular, were anticipated approvals for their respective makers. Both had previously been cleared for marketing in Europe.Given twice-yearly, Sunlenca is a first-of-its-kind drug that Gilead hopes can be used as both a treatment and preventive option for HIV. Its initial approval in the U.S. is for adults whose HIV infection can no longer be controlled by existing treatment regimens due to drug resistance, intolerance or safety reasons.Approval was supported by results from a trial called CAPELLA, which showed treatment with Sunlenca, when added to an antiviral regimen, pushed viral loads down to undetectable levels in 81% of patients with multidrug-resistant HIV.Sunlencas approval in the U.S. was held back by concerns about the potential for glass particles to form in vials of the drug that were made with borosilicate, leading to an initial FDA rejection in March. Gilead later switched vials.Approval of Roches Lunsumio, meanwhile, marks another milestone, as its the first bispecific antibody approved by the FDA that targets proteins known as CD3 and CD20. A group of competitors from AbbVie, Regeneron and Johnson & Johnson is lining up behind Roche, and the dual-binding drugs are viewed as the next step forward in lymphoma treatment.In the U.S., Lunsumio is cleared for adult patients with the most common slow-growing form of non-Hodgkin lymphoma who have previously received at least two systemic therapies. The FDA granted it an accelerated approval, meaning Roche must confirm its benefit in further clinical testing.TG Therapeutics Briumvi also targets the CD20 protein, which is found on B cells, but is for the autoimmune disease multiple sclerosis. In clinical testing, treatment with the drug led to lower annualized relapse rates than Sanofis drug Aubagio, but didnt significantly reduce the risk of worsening disability.The FDA had previously delayed its decision on Briumvi to review additional information submitted by TG Therapeutics. The New York-based biotechnology company had sought to win approval of Briumvis active drug ingredient, called ublituximab, in combination with another medicine for two types of leukemia, but in April withdrew its application after disappointing clinical trial data.New drug approvals by FDA's CDER office declined in 2022YearTotal CDER approvalsNotable drugs cleared202237Opdualag, Mounjaro, Relyvrio202150Lumakras, Aduhelm, Leqvio202053Zeposia, Evrysdi, Veklury201948Trikafta, Oxbryta, Enhertu201859Biktarvy, Onpattro, Vitrakvi201746Dupixent, Ocrevus, Hemlibra201622Tecentriq, Exondys 51, Spinraza201545Cosentyx, Ibrance, TagrissoSOURCE: FDA '