The Food and Drug Administration faced renewed scrutiny after two recent advisory committee meetings raised questions about its transparency and consistency, according to an Aug. 5 report. The meetings concerned Capricor Therapeutics’ Duchenne muscular dystrophy cardiomyopathy cell therapy and Replimune’s RP1 for advanced melanoma.
Mindy Leffler, a consultant and mother of a patient in the Phase 2 trial for deramiocel, criticized the FDA’s analysis presented to the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC), saying, “There were some really disingenuous things that were done to put together the analysis that they came up with.” The committee voted 9-3 against recommending approval of Capricor’s therapy. Leffler said her son’s cardiac function had stabilized since receiving treatment. Capricor CEO Linda Marbán expressed disappointment with the process and did not rule out legal action over how statistical analyses from their Phase 3 HOPE-3 trial were handled.
In contrast, Replimune received a more favorable vote from CTGTAC, which voted 10-3 in favor of approving RP1 for advanced melanoma. However, despite this positive outcome, the FDA has yet to issue a decision past its scheduled date. Michael Gibney reported that internal FDA practice typically requires decisions before weekends when deadlines fall on non-business days; as such, stakeholders are awaiting clarity on RP1's status.
The recent events follow efforts by Acting Commissioner Kyle Diamantas to repair relations with rare disease groups after previous leadership under Marty Makary and Vinay Prasad saw reversals in guidance and unexpected rejections of therapies including deramiocel and RP1. Temporary leaders reversed several prior decisions earlier this year: uniQure was allowed to pursue accelerated approval for its Huntington’s disease gene therapy based on existing data without additional trials; REGENXBIO planned resubmission of its Hunter syndrome gene therapy; Replimune was given an August action date for RP1 after prior rejections.
Despite these steps toward greater openness, both companies described communication gaps leading up to their respective adcomms. Marbán said Capricor was unaware of issues with its data until late June despite requesting meetings with FDA staff weeks ahead of time: “We have not gotten any issues that they want to discuss.” Misalignment persisted regarding which statistical plans or endpoints should be reviewed during committee deliberations.
As legal challenges loom following Capricor's negative outcome, and Replimune awaits word, questions remain about whether recent changes at the agency will restore industry trust or if uncertainty will persist.
