FDA Office Favors Antibody-drug Conjugate for Advanced Multiple Myeloma

An office of the U.S. Food and Drug Administration (FDA) has recommended that belantamab mafodotin, GlaxoSmithKline’s investigational antibody-drug conjugate, be approved for heavily pretreated relapsed or refractory multiple myeloma patients.

The recommendation by the FDA’s  Oncologic Drugs Advisory Committee is for patients who had at least four prior lines of treatment, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

If approved, belantamab mafodotin will be the first therapy of its class available for advanced multiple myeloma.

“We are pleased the committee recognized the potential for belantamab mafodotin to help patients who have relapsed or refractory multiple myeloma, an incurable disease with limited treatment options. We look forward to working with the FDA as they complete their review of our Biologics License Application,” Axel Hoos, senior vice president and head of Oncology Research and Development at GlaxoSmithKline (GSK), said in a press release.

Members of the committee participated in a virtual meeting on July 14 to review and discuss data supporting the investigational treatment’s application.

After reviewing data from the open-label DREAMM-2 Phase 2 trial (NCT03525678), which formed the basis of its support, the members agreed in a 12-0 vote that belantamab mafodotin’s benefits outweighed its risks for this patient group.

Belantamab mafodotin is an antibody-drug conjugate. As such, it is made up of an antibody that specifically recognizes the B-cell maturation antigen (BCMA) — a protein found on the surface of myeloma cells — and linked to the cancer-killing agent auristatin F. Once the antibody binds to cancer cells containing the BCMA protein, auristatin F is released into the cells, destroying them.

DREAMM-2 is  investigating the safety and efficacy of two doses of belantamab mafodotin (2.5 mg/kg or 3.4 mg/kg) given every three weeks to 196 people with heavily pretreated myeloma.

Six-month data from the study, published in The Lancet Oncology, showed that about one-third of patients responded to treatment with belantamab mafodotin, and more than half of responders in both dose groups attained very good partial responses or better.

However, the incidence of adverse events leading to death and the need for treatment adjustments were more frequent in patients on the treatment’s higher dose. GSK requested approval of its lower dose in its application.

The company also presented follow-up study data at the recent 2020 ASCO Annual Meeting, again showing that about one-third (32%) of patients on the lower dose (2.5 mg/kg) of belantamab mafodotin responded to treatment, with more than half (58%) achieving very good partial responses or better.

Responses lasted a median of 11 months, and patients lived for a median of 14.9 months. No new safety concerns were identified.

The FDA will consider the committee’s recommendation when making its decision on the approval request. The agency had designated belantamab mafodotin a breakthrough therapy in 2017, and granted its application priority review earlier this year.

The European Medicines Agency (EMA) is also reviewing, under accelerated assessment, a marketing authorisation application requesting belantamab mafodotin be approved for the same patient group in Europe.