FDA Update: Merck Action on Keytruda Gastric Cancer Indication Tops Busy Week

Merck will withdraw Keytruda's advanced gastric indication after an FDA panel vote, a drug with supply problems gets a new indication, NDAs for an HIV therapy, and other news.

Keytruda Gastric Cancer Indication to Cease. Merck announced late Thursday that it would voluntarily withdraw the U.S. accelerated approval indication for Keytruda (pembrolizumab) for certain patients with gastric cancer or gastroesophageal junction adenocarcinoma whose tumors express PD-L1, based on parameters of an FDA-approved test, who have seen their disease progress after at least two lines of therapy, including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, human epidermal growth factor receptor 2 (HER2)/neu-targeted therapy. The decision follows the April 29 hearing of the FDA Oncology Drugs Advisory Committee, where the panel recommended against continuing the indication. As agreed with the FDA, Merck will initiate the withdrawal in six months. The decision does not affect other indications for Keytruda.

FDA approval of Rylaze addresses supply issues. The FDA has approved Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) as a component of a chemotherapy regimen to treat acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients who are allergic to the E. coli-derived asparaginase products used most commonly for treatment. Jazz Pharmaceuticals, the therapy’s developer, expects Rylaze to be commercially available in mid-July.

The only other FDA-approved drug for such patients with allergic reactions has been under global shortage since 2016. Jazz Pharmaceuticals’ Erwinaze (asparaginase erwinia chrysanthemi) has experienced supply and manufacturing issues from the owner and manufacturer of the product, Porton Biopharma Limited.

FDA approves sNDA for STI trichomoniasis. The FDA has approved a supplemental New Drug Application (sNDA) to expand the use of Solosec (secnidazole) to include the treatment of adults with trichomoniasis, a sexually transmitted infection. The approval is based, in part, on trial results that demonstrated a clinically and statistically significant cure rate of 92.2% for patients with trichomoniasis treated with Solosec (n=64) as compared to placebo

The therapy, developed by Lupin Pharmaceuticals, was approved in the United States in 2017 for the treatment of bacterial vaginosis in adult women. The supplemental approval makes the product the first single-dose oral prescription antimicrobial agent approved for the treatment of both trichomoniasis and bacterial vaginosis.

Gilead submits NDA for HIV therapy lenacapavir. Gilead Sciences has submitted a New Drug Application (NDA) to the FDA seeking approval of lenacapavir, an investigational, long-acting HIV-1 capsid inhibitor, for the treatment of HIV-1 infection in heavily treated people with multi-drug resistant (MDR) HIV-1 infection.

The submission is supported by data from the phase 2/3 CAPELLA trial, which evaluated the safety and efficacy of lenacapavir administered subcutaneously every six months in combination with an optimized antiretroviral background regimen. Data on lenacapavir will be presented during the 11th International AIDS Society Conference on HIV Science in July 2021.

FDA accepts application for treatment for opioid addiction. The FDA has accepted Braeburn’s resubmitted New Drug Application (NDA) for Brixadi (buprenorphine) for moderate-to-severe opioid use disorder. The Prescription Drug User Fee Act date is December 15, 2021.

Brixadi is an extended-release injection for subcutaneous weekly and monthly use for patients who have initiated treatment with a single dose of a transmucosal buprenorphine product or who are already being treated with buprenorphine.

The resubmission is in response to a Complete Response Letter issued by the FDA in December 2020 citing deficiencies found during an inspection at a third-party manufacturing facility. Braeburn has worked closely with the third-party manufacturer to address the deficiencies identified in the Complete Response Letter, according to company officials. The letter did not cite any other deficiencies other than those related to third-party manufacturing.

During development, the safety Brixadi was consistent with the known safety profile of oral buprenorphine with the exception of mild-to-moderate injection-site reactions. The most common adverse reactions (occurring in ≥5% of patients) associated with BRIXADI administration included injection-site pain, headache, constipation, nausea, injection-site erythema, injection-site pruritus, insomnia and urinary tract infection.

Gene therapy for muscular dystrophy receives Fast Track designation. The FDA has granted Fast Track designation to Asklepios BioPharmaceutical’s LION-101 gene therapy program. LION-101 is a recombinant adeno-associated virus (rAAV) based vector being developed as a one-time intravenous infusion for the treatment of patients with limb-girdle muscular dystrophy type 2I/R9 (LGMD2I/R9).

LGMD2I/R9 is a rare form of muscular dystrophy that is caused by mutations in the FKRP gene. Symptoms often develop in late childhood and worsen over time.

AskBio, a subsidiary of Bayer, plans to begin U.S. trials of LION-101 in the first half of 2022. The gene therapy will be evaluated in a phase i/2 multicenter trial in adults and adolescents.

Glioblastoma therapy receives Fast Track designation. The FDA has granted Fast Track Designation to CNS Pharmaceuticals’berubicin for the treatment of patients with recurrent glioblastoma multiforme (GBM). Berubicin is an anthracycline, a class of anticancer agent that induces DNA damage in targeted cancer cells by interfering with the action of topoisomerase II, a critical enzyme enabling cell proliferation.

The company has initiated enrollment for a phase 2, adaptive, open label clinical trial in adults with GBM. A pre-planned, non-binding futility analysis will be performed after about 30% to 50% of all planned patients have completed the primary endpoint at six months. The company has also received FDA Orphan Drug designation.

Kite plans to submit supplemental BLA for Yescarta. Kite, a Gilead Company, has announced positive top-line results from the phase 3 ZUMA-7 trial of CAR T-cell therapy Yescarta (axicabtagene ciloleucel) in second-line relapsed or refractory large B-cell lymphoma. The trial met the primary endpoint of event-free survival, with a 60% reduction in the risk of disease progression, introduction of new lymphoma therapy or death over current standard of care, which is chemotherapy plus stem cell transplant.

Safety results from the study were consistent with or lower than the known safety profile of Yescarta for the treatment of LBCL in the third-line setting. Six percent of patients experienced cytokine release syndrome Grade 3 or higher, with a median onset of three days, and 21% experienced neurological events Grade 3 or higher. No new safety concerns were identified in this second-line setting.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy already available to treat adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma and adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.