FDA Extends Deramiocel Review for Duchenne Muscular Dystrophy After HOPE-3 Amendment

The FDA has extended the Prescription Drug User Fee Act (PDUFA) target action date for Capricor Therapeutics’ deramiocel, an investigational cell therapy for Duchenne muscular dystrophy (DMD), from August 22 to November 22, 2026.¹ The 3-month extension follows the agency’s acceptance of additional phase 3 HOPE-3 (NCT05126758) data as a major amendment to the biologics license application (BLA).²

“With an additional year of follow-up from HOPE-3, we now have one of the most extensive clinical datasets evaluating upper limb function in Duchenne,” Linda Marbán, PhD, chief executive officer of Capricor, said in a statement.¹ “HOPE-3 met its primary endpoint, demonstrating a statistically significant benefit in upper limb function, and we believe the additional open-label data and further analyses included in the amendment strengthen the evidence supporting a refined proposed indication. We appreciate the FDA’s continued engagement and look forward to working constructively with the agency as it completes its review.”

The amendment includes 24-month open-label extension findings and additional robustness analyses from HOPE-3. Capricor submitted the information after a July 2026 FDA advisory committee meeting and asked the agency to consider a refined proposed indication centered on preservation of upper limb function, the trial’s primary end point.¹

The FDA’s Center for Biologics Evaluation and Research accepted the amendment for review and classified it as major, prompting the revised action date. According to Capricor, the agency cited the substantial unmet need associated with DMD. The extension provides additional review time and does not indicate whether the BLA ultimately will be approved or what population and labeling might be authorized.

HOPE-3 enrolled 106 boys and young men with DMD, most nonambulatory, at a mean age of approximately 15 years; more than 75% had a clinical diagnosis of cardiomyopathy, and roughly 90% were already receiving cardiac medications at baseline.² Participants were randomized in double-blind fashion to intravenous deramiocel, 150 million cells, or placebo every 3 months for 12 months. The trial met its primary end point, a 54% slowing of decline on the Performance of Upper Limb, version 2.0 (PUL v2.0), in the intention-to-treat population (n = 105; P = .029), and its key secondary end point, a 91% slowing of decline in left ventricular ejection fraction (LVEF) by centrally read cardiac MRI (n = 83; P = .041).

READ MORE: Case Report Raises Questions About Cardiac Microdystrophin Expression, Safety Monitoring With Duchenne Gene Therapy

The most frequently reported adverse events were hypersensitivity reactions, managed prospectively with glucocorticoid and H1/H2-blocker pretreatment; no unexpected safety signals emerged in extended follow-up of the earlier HOPE-2 cohort. The program's rationale traces to the phase 2 HOPE-2 trial, in which deramiocel produced a 36.2-percentile advantage on mid-level elbow PUL 1.2 scores at 12 months (P = .014) and reduced the cardiac injury marker CK-MB by a 29.1-percentile difference (P = .025) versus placebo; open-label extension data showed sustained stabilization of LVEF among patients who entered with preserved cardiac function.

DMD is an X-linked disorder caused by the absence of functional dystrophin and is characterized by progressive skeletal, respiratory, and cardiac muscle degeneration. Capricor estimated that approximately 15,000 people in the United States have DMD, predominantly boys.¹ Progressive cardiomyopathy and heart failure are major contributors to mortality. Although available treatments may address selected disease mechanisms or complications, the company noted that DMD remains incurable and treatment options are limited.

Capricor's BLA was accepted for review in March 2025 under a PDUFA date of August 31, 2025, but the FDA issued a complete response letter in July 2025, citing insufficient evidence of effectiveness and unresolved chemistry, manufacturing, and controls elements.³ After Capricor incorporated the completed HOPE-3 dataset into a resubmission, the agency designated it a class 2 review with a August 22, 2026, PDUFA date.

An FDA advisory committee voted 9-3 against recommending approval on July 29, 2026, with reviewers and several panelists questioning revisions Capricor made to the trial's statistical analysis plan after randomization and expressing skepticism that LVEF functions as a validated surrogate of clinical benefit in this population; the panel also flagged a signal of increased left ventricular volume warranting further scrutiny.⁴ Company representatives and patient advocates argued that the totality of evidence, particularly the upper-limb functional data, combined with the absence of any alternative treatment, supported approval despite the panel's nonbinding recommendation.

Deramiocel consists of allogeneic cardiosphere-derived cells that exert immunomodulatory, antifibrotic, and regenerative paracrine effects on injured myocardium and skeletal muscle. The candidate has previously received US orphan drug, regenerative medicine advanced therapy, and rare pediatric disease designations, as well as orphan drug and advanced therapy medicinal product designations in Europe.

REFERENCES
1. Capricor Therapeutics announces extension of PDUFA target action date as FDA continues review of deramiocel BLA. Capricor Therapeutics. August 24, 2026. Accessed August 24, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/354/capricor-therapeutics-announces-extension-of-pdufa-target
2. McDonald CM, et al. Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. Published online July 29, 2026.
3. Capricor Therapeutics announces establishment of new PDUFA date for Deramiocel BLA. News release. Capricor Therapeutics. March 10, 2026. Accessed August 24, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/338/capricor-therapeutics-announces-establishment-of-new-pdufa
4. Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting; Establishment of a Public Docket. Federal Register. June 29, 2026. Accessed August 24, 2026. https://www.federalregister.gov/documents/2026/06/29/2026-13096/cellular-tissue-and-gene-therapies-advisory-committee-notice-of-meeting-establishment-of-a-public