FDA Advisory Committee Votes Against Deramiocel for DMD Cardiomyopathy

The FDA's Cellular, Tissue, and Gene Therapies Advisory Committee voted 9 to 3, with no abstentions, that the available evidence does not provide substantial evidence of effectiveness to recommend approval for deramiocel in treating cardiomyopathy in patients with Duchenne muscular dystrophy (DMD).¹ The vote is nonbinding, but it signals a difficult path ahead for Capricor Therapeutics' biologics license application (BLA) ahead of the FDA's August 22, 2026, PDUFA target action date.²

Committee vote and reasoning

Members who voted no generally cited concerns about the stability of the statistical results, saying that outcomes on the left ventricular ejection fraction (LVEF) endpoint, and to a lesser extent the upper-limb endpoint, appeared highly sensitive to how missing data were handled and which analytic assumptions were applied. Several said they had not seen evidence that LVEF, as measured in the trial, functions as a validated surrogate for clinical benefit in this population, and some noted that earlier versions of the sponsor's own statistical analysis had not met the prespecified endpoint.

A few members also raised questions about a potential safety signal related to increases in left ventricular volume that they said warranted further evaluation. Several no-voting members emphasized the significant unmet medical need in DMD cardiomyopathy and characterized their vote as reflecting the narrow scope of the question posed rather than a broader judgment on the therapy's underlying scientific rationale.

Members who voted yes generally argued that the totality of evidence, particularly the upper-limb functional data, supported approval, and expressed concern that the FDA's review had focused heavily on procedural and technical issues, including which statistical analysis plan version to use, rather than a full evaluation of the submitted data. These members pointed to the severity and rarity of the disease as reasons to apply greater regulatory flexibility, and cited testimony from patients and caregivers describing a lack of alternative treatment options as a significant factor in their decision.

Path to today's meeting

Mechanistically, deramiocel consists of allogeneic cardiosphere-derived cells. Its proposed mechanism is not dystrophin replacement; rather, the cells are described as exerting immunomodulatory and antifibrotic effects through secretion of extracellular vesicles that influence macrophage phenotype and inflammatory signaling. The therapy holds FDA orphan drug, regenerative medicine advanced therapy, and rare pediatric disease designations for DMD, along with orphan drug and advanced therapy medicinal product designations in Europe.³

Capricor completed its rolling BLA submission in January 2025, and the FDA accepted the application for priority review that March.^4,5 The original submission relied on data from the phase 2 HOPE-2 trial (NCT03406780), its open-label extension (NCT04428476), and comparisons to an FDA-funded natural history dataset.⁶

In July 2025, the FDA issued a complete response letter (CRL), stating the application did not meet the statutory requirement for substantial evidence of effectiveness; the agency wrote that HOPE-2 had not met its prespecified primary or secondary endpoints, and that post hoc analyses submitted to support the DMD cardiomyopathy indication were insufficient.^7,8

The FDA subsequently published the full CRL on its website. Capricor stated it had not been notified in advance, and noted the agency did not publish Capricor's response to the CRL alongside it, prompting the company to post its own response separately.^9,10 In that response, Capricor argued that HOPE-2's primary outcome was statistically significant "when analyzed with appropriate statistical techniques," and flagged that its planned resubmission might draw on additional data from the still-ongoing phase 3 HOPE-3 trial (NCT05126758).¹⁰ "Transparency is vital in regulatory communications, especially when patients are waiting for therapies with the potential to alter the course of devastating diseases such as Duchenne muscular dystrophy," Linda Marbán, PhD, chief executive officer of Capricor, said in a statement.⁹

Capricor reported topline results from HOPE-3 in December 2025.¹¹ The randomized, double-blind, placebo-controlled trial tested deramiocel, infused intravenously every 3 months for 12 months, against placebo in boys and young men with DMD across 20 US sites, with a mean participant age of approximately 15 years.⁶

According to the topline announcement, deramiocel met the primary endpoint, a 54% slowing of progression on Performance of Upper Limb total score (version 2.0) in the intent-to-treat population at 12 months (n = 105; P = .029), along with a 91% slowing of decline on the key secondary endpoint, left ventricular ejection fraction (n = 83; P = .041).¹¹ The FDA formally requested the complete HOPE-3 clinical study report in January 2026, without asking for additional trials or new patient data, and Capricor established a new PDUFA target action date of August 22, 2026, that March.^12,13

Dispute over HOPE-3's results

Two days before the advisory committee meeting, the FDA published briefing documents stating that HOPE-3 "did not meet its pre-specified primary and secondary efficacy endpoints, showing no statistically significant difference between deramiocel and placebo at 12 months."^14,15

The agency wrote that changes made to the trial's statistical analysis plan (SAP) after the randomized portion of the study concluded, generating at least two additional versions, altered the primary and key secondary endpoint definitions, analytical methods, and the data imputation strategy for certain intercurrent events. Reviewers also noted an imbalance in hypersensitivity reactions between arms (42% with deramiocel versus 15% with placebo), writing that this "raises the possibility that treatment assignment could be inferred even under formal blinding conditions."¹⁴

Capricor responded that its reported results were governed by a final SAP, version 3.0, finalized prior to unblinding, and that the post hoc analyses cited in the FDA's briefing materials relied on an earlier version the company described as "an unsigned incomplete internal draft" that predated a protocol amendment and did not reflect content the FDA had specifically requested.^15,16

"The Phase 3 HOPE-3 results demonstrate a statistically significant benefit on the primary endpoint, PUL 2.0, with supportive benefits in cardiac function, and we believe Deramiocel offers a meaningful treatment option for boys and young men living with Duchenne, who continue to face a significant unmet medical need," Marbán said in a statement.¹⁶

On the day of the advisory committee meeting, Capricor announced that The Lancet had published the full HOPE-3 results based on SAP 3.0, following independent peer review.^17,18 The publication reported the same 54% slowing of upper limb decline (P = .03) along with cardiac benefits, including reduced progression of myocardial scarring on cardiac MRI, and the study authors reported no deaths and infrequent serious adverse events during the trial.^18,19 Capricor said the publication "reinforces our confidence in the strength and durability of these results in advance of Deramiocel's PDUFA target action date of August 22.”¹⁷

FDA's presentation to the committee

At the meeting, FDA reviewers laid out the HOPE-3 SAP revision history in detail: an initial version (SAP 1.1) dated July 2022 was used for the FDA's own analysis, followed by a December 2023 revision (SAP 1.7), then two further versions dated September 2025 and November 2025 (SAP 2.0 and SAP 3.0), the latter finalized the same day the trial's database was locked and unblinded. Reviewers also cited the asymmetric rate of hypersensitivity reactions between arms (41.5% with deramiocel versus 15.4% with placebo) as a potential source of partial unblinding, separate from the SAP timeline.²⁰

On the statistical changes themselves, the FDA said the applicant's later analyses switched the primary endpoint from mean change to percent change from baseline, and the key secondary endpoint from a continuous measure to a ranked and then dichotomized version, changes reviewers said lacked persuasive scientific justification given that the underlying disease heterogeneity was known at the time the trial was designed. Reviewers also noted the applicant's revised secondary-endpoint analysis excluded 23 of 106 randomized subjects (22%) who lacked complete baseline and month 12 data, which the FDA said departed from the intent-to-treat principle.

Comparing analyses across SAP versions, the FDA showed that its own SAP 1.1 model found no significant difference between arms on either the primary endpoint (mean difference, 0.66; P = .24) or the key secondary endpoint (mean difference, -0.04%; nominal P = .97), and that a statistically significant result for the primary endpoint emerged only under the most recent, most heavily modified version of the analysis.

Reviewers concluded that neither HOPE-2 nor HOPE-3 met their prespecified primary or key secondary endpoints, that the post hoc analyses submitted by Capricor did not provide substantial evidence of effectiveness, and that the benefit-risk assessment for deramiocel was unfavorable in the absence of evidence of clinical benefit.²⁰

REFERENCES
1. Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting; Establishment of a Public Docket. Federal Register. June 29, 2026. Accessed July 29, 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
2. Capricor Therapeutics Announces FDA Advisory Committee Meeting to Review BLA for Deramiocel for the Treatment of Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. June 26, 2026. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/348/capricor-therapeutics-announces-fda-advisory-committee
3. Capricor Therapeutics. Pipeline: Duchenne Muscular Dystrophy Overview. Accessed July 29, 2026. https://www.capricor.com/pipeline/duchenne-muscular-dystrophy-overview
4. Capricor Therapeutics Completes Submission of Biologics License Application to the U.S. FDA for Deramiocel for the Treatment of Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. January 2, 2025. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/303/capricor-therapeutics-completes-submission-of-biologics
5. Capricor Therapeutics Announces FDA Acceptance and Priority Review of its Biologics License Application for Deramiocel to Treat Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. March 4, 2025. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/305/capricor-therapeutics-announces-fda-acceptance-and-priority
6. McDonald CM, Marbán E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022;399(10329):1049-1058. doi:10.1016/S0140-6736(22)00012-5
7. Capricor Therapeutics Provides Regulatory Update on Deramiocel BLA for Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. July 11, 2025. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/319/capricor-therapeutics-provides-regulatory-update-on
8. Complete Response. FDA. July 9, 2025. Accessed July 29, 2026. https://download.open.fda.gov/crl/CRL_BLA125842_20250709.pdf
9. Capricor Therapeutics Responds to FDA Posting of Complete Response Letter (CRL) for Deramiocel. News release. Capricor Therapeutics. September 9, 2025. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/325/capricor-therapeutics-responds-to-fda-posting-of-complete
10. Marbán L, Kayo MW. Response to 09 July 2025 Complete Response Letter. Capricor Therapeutics. July 16, 2025. Accessed July 29, 2026. https://d1io3yog0oux5.cloudfront.net/_482bc4203ea211827b4af3a98e815915/capricor/files/pages/capricor/db/2325/description/CAPR_response_letter_FINAL_%281%29.pdf
11. Capricor Therapeutics Announces Positive Topline Results from Pivotal Phase 3 HOPE-3 Study of Deramiocel in Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. December 3, 2025. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/331/capricor-therapeutics-announces-positive-topline-results
12. Capricor Therapeutics Provides Regulatory Update on Deramiocel BLA Following FDA Review of HOPE-3 Topline Data. News release. Capricor Therapeutics. January 20, 2026. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/335/capricor-therapeutics-provides-regulatory-update-on
13. Capricor Therapeutics Announces Establishment of New PDUFA Date for Deramiocel BLA. News release. Capricor Therapeutics. March 10, 2026. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/338/capricor-therapeutics-announces-establishment-of-new-pdufa
14. FDA Briefing Document: Cellular, Tissue, and Gene Therapies Advisory Committee Meeting, July 29, 2026. FDA. Accessed July 29, 2026. https://www.fda.gov/media/193839/download
15. McKenzie H. FDA Disputes Capricor's Claims of Phase 3 Success for DMD Cell Therapy. BioSpace. July 27, 2026. Accessed July 29, 2026. https://www.biospace.com/drug-development/fda-disputes-capricors-claims-of-phase-3-success-for-dmd-cell-therapy
16. Capricor Comments on Briefing Materials Ahead of July 29 FDA Advisory Committee Meeting for Deramiocel. News release. Capricor Therapeutics. July 27, 2026. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/349/capricor-comments-on-briefing-materials-ahead-of-july-29
17. The Lancet Publishes HOPE-3 Data for Capricor Therapeutics' Deramiocel in Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. July 29, 2026. Accessed July 29, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/350/the-lancet-publishes-hope-3-data-for-capricor
18. Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomized, double-blind, placebo-controlled trial. Lancet. 2026. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01385-1/fulltext
19. Phase 3 Trial Shows Investigational Cell Therapy Slowed Disease Progression in Duchenne Muscular Dystrophy. UC Davis Health. July 29, 2026. Accessed July 29, 2026. https://health.ucdavis.edu/welcome/news/headlines/phase-3-trial-shows-investigational-cell-therapy-slowed-disease-progression-in-duchenne-muscular-dystrophy/2026/07