Capricor Therapeutics Faces 9-3 AdCom Rejection for Deramiocel in Duchenne Cardiomyopathy

A lopsided advisory committee vote has placed Capricor Therapeutics' BLA resubmission for deramiocel under significant regulatory pressure ahead of the August 22, 2026 PDUFA date, with the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voting 9-3 that available evidence does not support the therapy's effectiveness for cardiomyopathy in Duchenne muscular dystrophy (DMD). For regulatory affairs leads tracking cell therapy BLA strategy, the vote's margin and the specific methodological objections raised by FDA reviewers carry implications well beyond this single application.

Deramiocel is an allogeneic cardiosphere-derived cell therapy administered by intravenous infusion every three months. The BLA resubmission, BLA 125842, drew on data from the phase 2 HOPE-2 trial and its open-label extension, alongside the pivotal phase 3 HOPE-3 study, a multicenter, randomized, double-blind, placebo-controlled trial enrolling 106 patients aged 10 and older with DMD. HOPE-3 met its primary endpoint: total Performance of the Upper Limb version 2.0 (PUL2.0) percentage change from baseline at 12 months showed a least-squares mean difference of 4.55% favoring deramiocel (95% CI, 0.47–8.63; P =.029). A prespecified secondary endpoint in the mid-level elbow domain also reached significance (P =.008).

The committee's skepticism centered on the cardiac secondary endpoints. FDA reviewers disputed the statistical basis for the left ventricular ejection fraction (LVEF) finding, citing a change to the statistical analysis plan made the day before database unblinding, a shift from direct LVEF change analysis to a ranked-change methodology. Reviewers also raised concerns about blinding integrity, noting that a differing adverse event profile, including hypersensitivity reactions in the deramiocel arm, may have compromised the blind. Capricor reported an absolute LVEF difference of approximately 2.4 percentage points favoring deramiocel and no imbalance in severe or serious adverse events through 12 months, but those characterizations did not resolve the agency's methodological objections.

The CTGTAC vote was non-binding and addressed a narrower indication than Capricor originally proposed; the committee did not vote on the therapy's overall benefit-risk profile. This marks Capricor's second regulatory setback for deramiocel following a complete response letter issued in July 2025. If approved despite the panel's recommendation, deramiocel would represent the first cell-based therapy indicated for DMD cardiomyopathy and the first product targeting both cardiac and skeletal muscle dysfunction in later-stage disease under 21 CFR Part 601 biologics licensing requirements.

For CGT manufacturers developing rare disease programs, the FDA's scrutiny of late statistical analysis plan amendments and blinding integrity signals a tightening standard for pivotal trial design that QA and regulatory teams should factor into pre-BLA alignment meetings with the agency.

The FDA's final decision on BLA 125842 remains due August 22, 2026, a date that will serve as a measurable indicator of how the agency weighs statistically significant functional endpoints against disputed cardiac biomarker methodology in allogeneic cell therapy submissions.

Source: CGTLive via CGTLive.com, August 14, 2026.