FDA approves first BCMA-targeted therapeutic

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The FDA has approved GlaxoSmithKline (GSK)’s belantamab mafodotin for relapsed or refractory multiple myeloma. The antibody–drug conjugate (ADC) is the first therapeutic from the crowded BCMA-targeted pipeline to secure approval.

BCMA, a member of the TNF-receptor superfamily, is expressed on normal B lymphocytes as well as on multiple myeloma cells. Despite early efforts to target BCMA with canonical monoclonal antibodies, early candidates did not have sufficient efficacy to move forward. In recent years, however, drug developers have had more success with ADCs, bispecific antibodies and CAR-T cell therapies.

The FDA’s accelerated approval of belantamab mafodotin, for patients with multiple myeloma who have had at least four prior therapies, was based on an open-label trial in 97 heavily pre-treated patients. The overall response rate in this trial was 31%, and 73% of responders had a response duration of at least 6 months. Common adverse reactions included corneal epithelium change, and a black box warning on the drug’s label notes the associated risk of severe vision loss.

GSK is still developing the ADC for earlier lines of therapy, and in combination with other agents. A benefit of the ADC approach is that it provides an off-the-shelf product.

BCMA-targeted CAR-T therapies that are made to order for each patient are also approaching the market, setting the stage for a modality showdown. Bristol Myers Squibb and Bluebird Bio resubmitted their idecabtagene vicleucel for FDA approval in July, following an earlier submission and refuse-to-file letter. Johnson & Johnson and partner Legend Biotech are expected to file their CAR-T therapy JNJ-4528 for approval by the end of the year.

BCMA is the second most popular defined cancer target in the global cell therapy pipeline, trailing only behind CD19.

Amgen’s BCMAxCD3-targeted bispecific T cell engager AMG 420, another off-the-shelf product, is in phase II trials.

Belantamab mafodotin is the ninth ADC to secure FDA approval.

Nature Reviews Drug Discovery 19, 659 (2020)

Updates & Corrections

  • Correction 01 October 2020: Belantamab mafodotin was incorrectly identified as the tenth ADC to secure FDA approval. It is the ninth.

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