Capricor Therapeutics (NASDAQ:CAPR) shares fell about 67% on Monday after US Food and Drug Administration (FDA) staff reviewers raised concerns about the evidence supporting the effectiveness of the company's experimental cell therapy, deramiocel, for Duchenne muscular dystrophy (DMD)-associated cardiomyopathy.
The FDA released briefing documents ahead of a July 29 meeting of its Cellular, Tissue, and Gene Therapies Advisory Committee, which will review the therapy's efficacy and overall risk-benefit profile before the agency's August 22 Prescription Drug User Fee Act (PDUFA) target action date.
FDA reviewers questioned changes Capricor made to its analysis after completion of its late-stage trial, noting the company switched its primary assessment of arm function from raw scores on a 42-point scale to percentage change. The agency wrote that it did not consider the conversion "scientifically justified," saying it added complexity and reduced accuracy.
The reviewers also highlighted changes to the analysis of heart function, which shifted from measuring changes in left ventricular ejection fraction to ranking patients' results.
In addition, FDA staff questioned whether patients enrolled in the study had DMD-related cardiomyopathy, noting they had normal heart-pumping function on average at baseline. The reviewers also said evidence was limited that enough of the intravenously administered therapy reached the heart to produce a meaningful benefit.
Deramiocel is being reviewed under a biologics license application supported by data from the Phase 2 HOPE-2 trial, its long-term extension study, and the Phase 3 HOPE-3 trial.
In announcing the advisory committee meeting last month, Capricor said the application was supported by statistically significant results on the Phase 3 trial's primary endpoint, key secondary cardiac endpoint and other controlled secondary endpoints. The company said it remained confident in the overall evidence supporting deramiocel and its potential as a first-in-class treatment for Duchenne muscular dystrophy.
There are currently no FDA-approved therapies specifically for DMD-associated cardiomyopathy. Existing Duchenne treatments, including Sarepta Therapeutics' gene therapy Elevidys and exon-skipping drugs, target the underlying genetic cause of the disease rather than the heart complications that develop as it progresses.