FDA Updates for the Week of November 21, 2022


The FDA has approved a $3.5 million hemophilia B gene therapy and warned about Prolia in patients with kidney disease. The agency accepted for priority review two BLAs: for a dengue vaccine and for epcoritamab for large B-cell lymphoma. Additionally, GSK has pulled Blenrep from the U.S. market at the request of the FDA.

FDA approves $3.5 million gene therapy Hemgenix for hemophilia B.

The FDA has approved CSL Behring’s Hemgenix (etranacogene dezaparvovec) to treat adults with hemophilia B who currently use factor IX prophylaxis therapy, or have current or historical life-threatening hemorrhage.

Hemophilia B is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps blood clots form. Treatments for moderate-to-severe hemophilia B include prophylactic infusions of factor IX replacement therapy to temporarily replace or supplement low levels of blood-clotting factor.

Hemgenix is an adeno-associated virus vector-based gene therapy and is a one-time product given as a single dose by IV infusion. The therapy uses an adeno-associated virus as a vector that carries the Padua gene variant of Factor IX, which generates factor IX proteins. The gene is expressed in the liver to produce factor IX protein to increase blood levels of factor IX to limit bleeding episodes.

CSL Behring will begin commercializing Hemgenix as soon as possible in the United States with a list price of $3.5 million.

GSK pulls Blenrep from U.S. market.

GSK is withdrawing Blenrep (belantamab mafodotin-blmf) from the U.S. market at the request of the FDA. The agency made the request after the DREAMM-3 phase 3 confirmatory trial failed to meet its endpoints. Blenrep is a monotherapy treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies.

DREAMM-3, a head-to-head superiority trial of Blenrep monotherapy versus pomalidomide in combination with low dose dexamethasone, did not meet its primary endpoint of progression-free survival (PFS), the company recently announced. The primary endpoint of progression-free survival demonstrated a hazard ratio of 1.03. A hazard ration of more than 1 indicates an increased risk of harm.

Patients already enrolled in the Blenrep Risk Evaluation and Mitigation Strategy (REMS) program will have the option to enroll in a compassionate use program to continue to access treatment.

The FDA had granted accelerated approval of Blenrep in August 2020 based on the DREAMM-2 endpoint of overall response rate. It was the first in a new class of drugs known as anti-BCMA (B-cell maturation antigen) monoclonal antibodies. The BCMA pathway has been shown to be important for myeloma cell growth and survival.

FDA warns about Prolia in patients with kidney disease

The FDA is investigating the risk of severe hypocalcemia with serious outcomes, including hospitalization and death, in patients with advanced kidney disease on dialysis treated with Amgen’s osteoporosis therapy Prolia (denosumab).

The agency’s review of interim results from an ongoing safety study of Prolia suggests an increased risk of low calcium levels in the blood in patients with advanced kidney disease. Preliminary results from a separate internal FDA study further investigating hypocalcemia in dialysis patients treated with Prolia show a substantial risk with serious outcomes, including hospitalization and death. In addition, adverse event reports submitted to FDA showed severe and symptomatic hypocalcemia, including hospitalization and death, is occurring in patients with advanced kidney disease treated with Prolia,

Prolia works by blocking a protein called RANK (receptor activator of nuclear factor kappa beta) and helps prevent bone cells called osteoclasts from breaking down bone in the body. Prolia is administered by injection once every six months.

FDA accepts for priority review BLA for epcoritamab.

The FDA has accepted for priority review AbbVie’s biologics license application for epcoritamab to treat adult patients with relapsed/refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. The Prescription Drug User Fee Act (PDUFA) date is May 21, 2023.

Epcoritamab is an investigational subcutaneous bispecific antibody being co-developed by AbbVie and Genmab. It was created using Genmab’s DuoBody technology, which is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B-cells and induces T cell mediated killing of CD20+ cells. CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies.

The application is supported by results from the large B-cell lymphoma cohort of the EPCORE phase 1/2 trial evaluating the safety and preliminary efficacy of investigational epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma.

FDA grants priority review of BLA for dengue vaccine.

The FDA has granted priority review of the Takeda’s biologics license application (BLA) for TAK-003, the company’s investigational dengue vaccine candidate. TAK-003 is being evaluated for the prevention of dengue disease caused by any dengue virus serotype in people 4 years through 60 years of age.

Dengue is a mosquito-borne virus endemic in more than 125 countries, including the U.S. territories of Puerto Rico, the U.S. Virgin Islands and American Samoa. Incidence of dengue has increased globally over the past two decades and is a leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia.

The BLA is supported by safety and efficacy data from the pivotal phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, where the dengue vaccine candidate met its primary endpoint by preventing 80.2% of symptomatic dengue cases at 12 months. In addition, TAK-003 met its secondary endpoint by preventing 90.4% of hospitalizations at 18 months, and in an exploratory analysis, it demonstrated protection against dengue fever through 4.5 years (54 months) after vaccination.

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