The US FDA's Cellular, Tissue and Gene Therapies Advisory Committee (CTGTAC) voted 9 to 3 against the effectiveness of deramiocel (CAP-1002) for the treatment of cardiomyopathy in patients with Duchenne muscular dystrophy (DMD), delivering a setback to San Diego-based Capricor Therapeutics (Nasdaq: CAPR) ahead of an August 22 Prescription Drug User Fee Act (PDUFA) target action date. No approved therapy currently exists for DMD-associated cardiomyopathy, which is the leading cause of death in the disease.
The committee's vote is non-binding, and the US FDA retains the authority to approve or reject the Biologics License Application (BLA) independent of the panel's recommendation. Capricor said it remains focused on working with the agency toward potential approval before the PDUFA date.
Importantly, the CTGTAC's voting question addressed a narrower indication than Capricor had originally proposed — limited to cardiomyopathy — and did not encompass a broader benefit-risk assessment of deramiocel. In a separate discussion on upper limb function, committee feedback was described by Capricor as directionally supportive of the clinical evidence from the Phase III HOPE-3 trial, including results on its primary endpoint, the Performance of Upper Limb version 2.0 (PUL 2.0) scale. The HOPE-3 data, published in The Lancet the day before the advisory meeting, showed deramiocel slowed upper limb function decline by 54% versus placebo (p=0.03) in the randomized, double-blind, placebo-controlled trial of 106 patients.
The split between the committee's skepticism on cardiac endpoints and its more favorable view of skeletal muscle data reflects a tension that had been flagged in the FDA's pre-meeting briefing documents, which raised questions about the strength of the cardiac evidence supporting the BLA. Capricor had acknowledged the briefing materials ahead of the meeting, while maintaining confidence in the overall clinical package.
Deramiocel consists of allogeneic cardiosphere-derived cells (CDCs), which act by secreting exosomes that target macrophages and shift their phenotype toward a pro-healing, anti-inflammatory state. The mechanism is intended to slow fibrotic and inflammatory damage in both cardiac and skeletal muscle. The therapy has received Orphan Drug Designation from both the US FDA and the European Medicines Agency (EMA), along with Regenerative Medicine Advanced Therapy (RMAT) designation and Rare Pediatric Disease Designation in the US — the latter of which may qualify Capricor for a Priority Review Voucher upon approval.