The Food and Drug Administration is facing renewed scrutiny after recent briefing documents appeared to reiterate earlier objections to two promising therapies aimed at treating late-stage melanoma and Duchenne muscular dystrophy. The agency’s internal debate highlights ongoing tensions over the approval process for innovative treatments for life-threatening and rare diseases.

Earlier this year, President Donald Trump replaced FDA officials Marty Makary and Vinay Prasad, whose tenure was marked by several high-profile rejections of breakthrough therapies. Since then, under acting Commissioner Kyle Diamantas, the agency seemed to be shifting toward reconsidering previously rejected applications and engaging outside experts in public hearings. However, the latest briefing papers released ahead of upcoming advisory committee meetings suggest some FDA staff continue to resist these therapies.

One such treatment is Replimune’s RP1, an immunotherapy for metastatic melanoma. RP1’s initial trial results indicated that about one-third of patients whose cancer had progressed despite prior immunotherapies achieved remission, with complete disappearance of tumors in roughly one-sixth of cases. Melanoma specialists have described these findings as unprecedented. Despite this, Dr. Prasad previously overruled the original review panel’s recommendation for approval. Subsequently, a new review panel endorsed the rejection, citing questions about the trial’s data—including speculation that tumor regression might be attributed to biopsy procedures rather than the therapy itself.

The FDA staff’s latest briefing revisits these concerns and applies analytical methods that critics characterize as discounting positive outcomes. For example, efficacy calculations excluded certain patients from the numerator but included them in the denominator, resulting in a reported response rate drop from 33.6% to 15.7%. The briefing acknowledged that patients who benefited from RP1 experienced a median progression-free survival of 30.6 months compared to 4.4 months on prior treatments, yet described this as “uninterpretable.” The agency maintained that a randomized controlled trial would be necessary to confirm efficacy, despite arguments that such a trial might be unethical given the limited treatment options and severity of disease in this population.

Separately, Capricor Therapeutics has resubmitted an application for a cell therapy targeting advanced Duchenne muscular dystrophy. The company previously faced rejection last summer when the FDA found its initial placebo-controlled trial too small to definitively establish benefit. The new trial involved a larger group of mostly wheelchair-bound patients and reported a 54% slowing in the decline of arm mobility and a 91% reduction in cardiac muscle weakening.

The FDA staff raised concerns that Capricor changed its statistical analysis methodology mid-trial, which the company attributes to guidance received from the agency prior to unblinding the study results. The FDA also questioned the trial’s blinding, suggesting that side effects might have revealed treatment assignments to patients, potentially biasing cardiac MRI assessments. Capricor has rejected these claims, emphasizing adherence to FDA protocols and suggesting the rejection may partly reflect retaliation for the company’s public criticism of the agency’s earlier decision.

This internal conflict within the FDA underscores ongoing challenges in balancing regulatory rigor with expedited access to treatments for serious conditions. Observers note that continued leadership vacuums and divergent views within the agency complicate the approval process. The advisory panels scheduled to review these therapies in the coming days will be closely watched indicators of the agency’s evolving stance on innovative medical treatments.