An FDA advisory committee has voted against approving Capricor Therapeutics’ cell therapy deramiocel for treatment of cardiomyopathy in patients with Duchenne muscular dystrophy, citing “fragile” efficacy data and statistical and study design issues as being behind their decision.
The Cellular, Tissue, and Gene Therapies Advisory Committee voted to reject the therapy 9 votes to 3. That vote is nonbinding, but it strongly signals a difficult path ahead for the company and deramiocel before the FDA’s August 22 decision date on whether to approve the therapy.
In the committee meeting, which is open for interested parties to view online, 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 testing deramiocel, a heart-cell derived therapy, in patients with Duchenne muscular dystrophy aged 10 years or older was published this week. 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%. The key cardiac endpoint, change in left ventricular ejection fraction (LVEF), did not reach statistical significance in the overall cardiac‑evaluable cohort, but 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, and loss of arm function is a major driver of daily disability in late‑stage Duchenne.
However, because the company 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 rather than assessing if it improved upper limb function.
Capricor previously submitted data from an earlier trial HOPE-2 and an open label extension to the FDA for this indication, but the earlier biologics license application was rejected by the regulator. This resubmission includes the new data from HOPE-3.
In a briefing document released by the regulator before the meeting, FDA reviewers say Capricor made statistical analysis plan changes after the HOPE-3 trial ended that make interpreting the analysis difficult and criticized the companies approach to handling missing data for some people in the placebo group. They also say the efficacy signal for cardiac improvement is “fragile.”
FDA reviewers noted in the document 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. They also highlighted that 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.
“We remain committed to deramiocel and to the patients who could benefit from it,” said Linda Marbán, PhD, chief executive officer of Capricor. “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, underscoring the unmet need within the Duchenne community. We remain focused on working with the FDA toward potential approval ahead of our August 22, 2026, PDUFA target action date.”
