Panel Rejects Capricor Cell Therapy Treatment

The FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee has voted against approving Capricor Therapeutics’ cell therapy deramiocel for treating cardiomyopathy in patients with Duchenne muscular dystrophy, citing “fragile” efficacy data and statistical and study design issues.

The committee voted 9 to 3 to reject the therapy, a decision that is nonbinding but signals a difficult path ahead for Capricor Therapeutics and deramiocel before the FDA’s August 22 decision date.

One of the committee members, Cynthia Tifft, MD, PhD, a senior clinician at the National Human Genome Research Institute, said: “If it was a bigger study, if it went for longer, if we chose different endpoints, there probably is something there. But given the question that was asked, I think the evidence is really not that compelling.”

The HOPE-3 Phase III trial tested deramiocel, a heart-cell derived therapy, in patients with Duchenne muscular dystrophy aged 10 years or older. Overall, 106 patients were randomly assigned to treatment with deramiocel or placebo, 83 of whom had evidence of cardiomyopathy at the beginning of the study.

The results of HOPE-3 show that deramiocel significantly slowed decline in upper-limb function, meeting the trial’s prespecified primary endpoint and slowing upper limb disease progression by about 54%. However, the key cardiac endpoint, change in left ventricular ejection fraction (LVEF), did not reach statistical significance in the overall cardiac-evaluable cohort.

A prespecified subgroup with documented cardiomyopathy showed a nominally significant benefit. Capricor and the researchers working on developing the therapy made upper-limb function the primary endpoint of the trial because deramiocel is intended to be a systemic therapy with both skeletal-muscle and cardiac benefits.

Loss of arm function is a major driver of daily disability in late-stage Duchenne. However, because Capricor is asking the FDA to approve the therapy for treatment of cardiomyopathy in patients with Duchenne, the committee met to discuss if deramiocel should be approved for this specific cardiac indication.

FDA reviewers say Capricor made statistical analysis plan changes after the HOPE-3 trial ended that make interpreting the analysis difficult. They also criticized the company’s approach to handling missing data for some people in the placebo group.

They noted that most HOPE-3 patients had relatively preserved cardiac function at baseline (mean LVEF 57%), which they felt limited conclusions about treatment of established Duchenne cardiomyopathy. Hypersensitivity reactions were far more frequent with deramiocel (42% vs 15% on placebo), which might have affected how patients and clinicians reported or measured improvements in functions that depend on effort, like arm and hand use.

Linda Marbán, PhD, chief executive officer of Capricor, said: “We remain committed to deramiocel and to the patients who could benefit from it. The Advisory Committee gave us an important opportunity to present the clinical evidence, and we were encouraged by the Committee’s discussion of deramiocel’s impact on skeletal muscle.”

In a moving open public hearing, patients, families, and clinicians shared their experience with the therapy, highlighting the unmet need within the Duchenne community. Capricor remains focused on working with the FDA toward potential approval ahead of their August 22, 2026, PDUFA target action date.