The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) voted 9 to 3, with no abstentions, that available evidence does not support the effectiveness of deramiocel for treating cardiomyopathy in patients with Duchenne muscular dystrophy (DMD). Deramiocel (Capricor Therapeutics) is an allogeneic cardiosphere-derived cell therapy administered by intravenous infusion every 3 months. The committee's non-binding vote addressed a narrower indication than Capricor proposed and did not include a vote on deramiocel's overall benefit-risk profile.
The vote marks Capricor's second regulatory setback for deramiocel, following a complete response letter in July 2025. If approved, deramiocel would become the first cell-based therapy indicated for DMD cardiomyopathy and the first product to target both cardiac and skeletal muscle dysfunction in later-stage disease. The FDA's target action date under the current Biologics License Application resubmission, BLA 125842, is August 22, 2026.
HOPE-3 trial design and primary endpoint results
The BLA under review included data from the phase 2 HOPE-2 trial (NCT03406780), its open-label extension HOPE-2-OLE (NCT04428476), and the pivotal phase 3 HOPE-3 trial (NCT05126758). HOPE-3 was a multicenter, randomized 1:1, double-blind, placebo-controlled study enrolling 106 patients with DMD aged 10 years and older, assigned to deramiocel (n=54) or placebo (n=52) between June 2022 and May 2024. Participants received deramiocel at 1.5×10⁸ cells or placebo by intravenous infusion over 60 to 90 minutes every 3 months for 12 months.
The primary endpoint, total Performance of the Upper Limb version 2.0 (PUL2.0) percentage change from baseline at 12 months, favored deramiocel by a least-squares mean difference of 4.55% (95% CI, 0.47-8.63; P = .029), meeting statistical significance. Capricor characterized the finding as a 54% slowing of upper limb function decline relative to placebo. The mid-level elbow domain of PUL2.0, a type I error-controlled secondary endpoint, showed an 8.12% difference favoring deramiocel (P = .008).
Cardiac secondary endpoints, safety profile, and the FDA's statistical dispute
Key secondary cardiac endpoints assessed left ventricular ejection fraction (LVEF) by cardiac MRI and myocardial scarring by late gadolinium enhancement. Capricor reported a statistically significant rank-change difference in LVEF favoring deramiocel, corresponding to an absolute LVEF difference of approximately 2.4 percentage points, along with significant differences on a prespecified cardiac global statistical test. Investigators reported no imbalance in severe or serious adverse events between the deramiocel and placebo groups through 12 months.
Frequently Asked Questions
What did the FDA advisory committee decide about deramiocel?
The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee voted 9 to 3 that available evidence does not support deramiocel's effectiveness for DMD cardiomyopathy; the vote is non-binding, and an FDA decision is expected by August 22, 2026.
What did the HOPE-3 trial show?
HOPE-3 met its primary endpoint, showing a 4.55% least-squares mean difference favoring deramiocel on total PUL2.0 score at 12 months (P = .029), with a statistically significant secondary LVEF benefit reported by Capricor.
Why did the FDA dispute the trial's statistical findings?
FDA reviewers questioned a late change to the statistical analysis plan for the LVEF endpoint and raised concerns about blinding integrity, citing a differing adverse event profile, including hypersensitivity reactions, between treatment groups.
The FDA's review disputed the statistical basis for the LVEF finding. Reviewers noted Capricor changed its statistical analysis plan the day before database unblinding, shifting from a direct analysis of LVEF change to a ranked-change analysis using a different test. The agency's briefing materials referenced an earlier analysis plan version, which Capricor described as an unsigned, incomplete internal draft superseded by the trial's addition of cohort B and by the company's final governing analysis plan, finalized before unblinding.
FDA reviewers also raised questions about the integrity of blinding in HOPE-3, citing a distinctive adverse event profile, including hypersensitivity reactions, differing between treatment groups. The FDA review team's briefing materials stated: "After extensive analyses of the submitted data both in the original BLA and in the BLA resubmission, the FDA review team was unable to identify a subpopulation that may potentially derive benefit from deramiocel."
"We remain confident in the strength of the HOPE-3 data," Linda Marbán, PhD, chief executive officer of Capricor Therapeutics, told CGTLive® in a statement. "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."
DMD-associated cardiomyopathy remains a leading contributor to morbidity and mortality in Duchenne, and no FDA-approved therapy is currently indicated specifically for the condition. Although not bound to the committee's recommendation, the FDA typically weighs advisory committee votes heavily in its final decisions, and a negative vote often signals a difficult approval path. The agency's decision on deramiocel is expected by the August 22, 2026, PDUFA target action date.
References
FDA Advisory Committee Votes Against Deramiocel for DMD Cardiomyopathy. The Cardiology Advisor. August 2026. https://www.thecardiologyadvisor.com/news/fda-advisory-committee-votes-against-deramiocel-dmd-cardiomyopathy/
Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomised, double-blind, placebo-controlled trial. The Lancet. 2026. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01385-1/fulltext
Capricor Therapeutics Provides Update on FDA Advisory Committee Meeting for Deramiocel. News release. Capricor Therapeutics. July 30, 2026. https://www.globenewswire.com/news-release/2026/07/30/3336165/0/en/Capricor-Therapeutics-Provides-Update-on-FDA-Advisory-Committee-Meeting-for-Deramiocel.html
FDA Disputes Capricor's Phase 3 Efficacy Claims for Duchenne Cell Therapy Deramiocel. BioPharm International. August 2026. https://www.biopharminternational.com/view/fda-disputes-capricor-s-phase-3-efficacy-claims-for-duchenne-cell-therapy-deramiocel
