Will Belantamab Mafodotin Get a Second Chance at Approval in Multiple Myeloma?

On Thursday, July 17, 2025. the FDA's Oncologic Drug Advisory Committee (ODAC) will convene to discuss the biologics license application (BLA) of belantamab mafodotin (Blenrep) for the treatment of adults with multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least 1 prior line of therapy and in combination with pomalidomide and dexamethasone in patients who have received at least 1 prior line of therapy including lenalidomide.

In an interview with Targeted Oncology, George Mulligan, PhD, chief scientific officer of the Multiple Myeloma Research Foundation (MMRF) provides background on belantamab's regulatory history and insight on what the ODAC's meeting could revolve around.

Belantamab mafodotin has had a notable and somewhat complex regulatory journey, particularly due to its accelerated approval status and subsequent withdrawal and re-evaluation.

Initially, belantamab mafodotin, a first-in-class BCMA-directed antibody-drug conjugate, received accelerated approval from the FDA on August 5, 2020, for adult patients with relapsed or refractory multiple myeloma who had received at least 4 prior therapies. This approval was based on data from the DREAMM-2 trial, which showed a clinically meaningful overall response rate (ORR) of 31%. The FDA also granted it priority review, orphan drug, and breakthrough therapy designations. As part of this accelerated approval, continued marketing was contingent upon verification of clinical benefit in confirmatory trials. A significant side effect identified was ocular toxicity, which led to a boxed warning in the prescribing information and a Risk Evaluation and Mitigation Strategy (REMS) program.

However, the regulatory path took a turn when the confirmatory phase 3 DREAMM-3 trial did not meet its primary end point of demonstrating superior progression-free survival (PFS) compared with a standard of care regimen. Consequently, in November 2022, GSK (the manufacturer) initiated the process for withdrawal of the United States marketing authorization for belantamab mafodotin at the request of the FDA.

More recently, based on positive results from 2 other phase 3 head-to-head trials, DREAMM-7 and DREAMM-8, which showed statistically significant and clinically meaningful improvements in PFS when belantamab mafodotin was used in combination therapies, the FDA accepted a BLA for belantamab mafodotin in combination with these regimens, with a US decision expected by July 23, 2025. These new applications are based on the robust data from the DREAMM-7 and DREAMM-8 trials, which also showed a positive trend in overall survival in DREAMM-7.