FDA advisers vote against approval of Capricor’s DMD therapy in chaotic adcomm meeting

News FDA FDA advisers vote against approval of Capricor’s DMD therapy in chaotic adcomm meeting July 29, 2026 | 8 min read | Heather McKenzie Twitter LinkedIn Facebook Email Print During a perplexing advisory committee meeting in which FDA reviewers focused largely on the Phase 3 HOPE-3 trial’s secondary endpoint of cardiac function, experts pointed to “very fragile” data. The committee voted 9-3 against approval of deramiocel. Capricor Therapeutics’ Duchenne muscular therapy cell therapy was voted down by an FDA advisory committee on Wednesday, with the biotech’s CEO expressing her frustration about the agency’s review of a draft statistical analysis plan that was never meant to be considered in the approval application.Capricor CEO Linda Marbán did not mince words when she kicked off the company’s presentation in support of deramiocel, which is currently under its second review at the FDA after being rejected a year ago.“When I first read the FDA’s briefing document, parts of it were so hard to reconcile with what actually occurred,” she told the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) Wednesday morning.

But Marbán failed to convince the committee members, who voted 9-3 against recommending approval of deramiocel after the contentious meeting.The FDA is not obligated to follow the recommendations of its advisory committees, though it often does. “The word of the day seems to be fragile. The results were very fragile,” said Janet Turk Wittes of Wittes, LLC, an expert in randomized controlled trials and a member of the committee.

“I simply didn’t see enough evidence of benefit to vote yes.”Those who voted no seemed to be challenged by the decision, given the unmet need and the painful testimony of families impacted by DMD from earlier in the day. Committee member Cynthia Tifft expressed her own frustrations with the phrasing of the voting question: Does the available evidence provide substantial evidence of effectiveness of deramiocel for the treatment of cardiomyopathy in patients with DMD? Tifft serves as the deputy clinical director and senior clinician director for the pediatric undiagnosed diseases program at the National Genome Research Institute.“Given the question that was asked, I think the evidence is really not that compelling, and I say that as a researcher who is in the middle of a gene therapy trial for an even rarer disease that is uniformly fatal.

So I get it,” Tifft said, explaining her no vote.Deramiocel did find some supporters on the committee. Patient representative Christopher Mariano Cassidy, Jr. took issue with the FDA’s decision to use the outdated statistical analysis plan.“So much of [the FDA’s reliability report] is devoted to identifying technicalities and procedural errors and using them as a basis for dismissing entire data sets out of hand without even examining,” Cassidy said.Another patient advocate, Debra Dunn, voted yes but expressed skepticism: “Am I 100% vested in that?

I don’t know ... listening to the patients and to their families. I’m a mom.

I have a heart. They don’t have an alternative.” A regulatory rollercoaster The FDA rejected deramiocel last July, saying in its complete response letter (CRL) that the Phase 2 data supporting the cell therapy fell short of the “statutory requirement for substantial evidence of effectiveness.”Capricor’s fortunes appeared to be turning around, however, when the biotech reported in December 2025 that deramiocel had hit both the primary and secondary endpoints in the pivotal Phase III HOPE-3 trial. In March, the treatment appeared to be back on track when the FDA accepted the company’s resubmission and set a target action date of August 22.

Duchenne muscular dystrophy Capricor Shares Rise as FDA Sets August Decision Date for Rejected Duchenne Therapy Capricor Therapeutics’ deramiocel was rejected in July 2025, potentially caught between Nicole Verdun, a former top biologics regulator at the FDA, and outgoing Vinay Prasad, director of the Center for Biologics Evaluation and Research. March 11, 2026 · 2 min read · Tristan Manalac Read more But on Monday, the picture again grew hazy. In briefing documents ahead of the adcomm, the FDA contended that the therapy did not in fact meet HOPE-3’s prespecified primary and secondary efficacy endpoints, “showing no statistically significant difference between deramiocel and placebo at 12 months.”Interpretation of the data was another key topic of conversation during the adcomm, with much discussion about cardiac imaging capabilities.“The results on cardiac imaging parameters taken together are difficult to interpret and do not appear to provide conclusive evidence of a favorable effect of deramiocel on slowing the decline of cardiac function in the studied population,” the FDA concluded in its briefing documents.From the beginning, the adcomm focused on the discrepancy between Capricor and the FDA over which statistical analysis plan (SAP) should have been prioritized for review.In its briefing documents, FDA reviewers posited that the final version of SAP version 3.0—dated Nov.

24, 2025—was not submitted to the regulator for review prior to Capricor’s biologics license application (BLA) resubmission, “and was not discussed and consequently not agreed upon.”The reviewers added that the process for SAP changes outlined in the HOPE-3 study’s prespecified blinding plan was not followed and that the final clinical study protocol (Protocol 9.0) deviated from the associated SAP 3.0.Marbán disagreed with this assertion and said on Monday ahead of the adcomm that the results “are governed by the final analysis plan, SAP version 3.0, which was finalized prior to unblinding” of the Phase 3 HOPE-3 study. Instead, the FDA analyzed the data using SAP version 1.1, Marbán told BioSpace on Monday, calling this version a draft. FDA UPDATE: FDA disputes Capricor’s claims of Phase 3 success for DMD cell therapy In briefing documents published Monday ahead of an advisory committee meeting for deramiocel, the FDA disagreed with Capricor’s assertion that a Phase 3 trial met its primary outcome measures.

July 27, 2026 · 3 min read · Heather McKenzie Read more “For reasons we do not understand why, the FDA has seized upon that unfinished, unsigned draft SAP and performed numerous analyzes based on this incomplete draft,” the CEO said on Wednesday. “This would be like your professor grading your term paper on an early draft you have never even submitted.”Marbán noted that after submitting SAP version 2.0, Capricor did not receive feedback from the FDA.“With receipt and distribution confirmed by the FDA, we were confident that they were supportive of our plan,” she said. After realizing that the sample size was smaller for the cardiac endpoint—left ventricular ejection fraction (LVEF), a measure of systolic function—this analysis was changed to be rank based, which Marbán said is less sensitive to outliers.

That change comprised SAP version 3.0The FDA, in its presentation, contended that SAP version 3.0 was finalized after the study’s unblinding. FDA Biostatistical Analyst Tingting Zhou laid out the agency’s two primary statistical concerns: that there were “late changes to the statistical analysis plan that lack adequate scientific justification,” and secondly, “the study conclusions lack robustness.” She added that the FDA used SAP version 1.1 as its “benchmark” because it was the SAP in place when the study initiated. The ultimate objective Marbán also addressed questions at the meeting regarding how HOPE-3’s endpoints were defined.

Capricor is proposing deramiocel for the treatment of upper limb impairment and/or cardiomyopathy in people with DMD who are nine years and older.Here as well, there was discord as the FDA asked its advisors to vote on whether “the available evidence from the HOPE-3 study provide substantial evidence of effectiveness of deramiocel for the treatment of cardiomyopathy in DMD.”The confusion over the cell therapy’s ultimate objective is not new.In 2024, following a pre-BLA meeting, the FDA’s cardiology reviewers suggested Capricor file a cardiac-focused BLA based on the results of HOPE-2 and a published natural trajectory of DMD cardiomyopathy, Marbán explained. Cardiomyopathy is the leading cause of death for patients with DMD.This change “was ultimately never implemented,” she said, “and a year ago, we received a complete response letter.”The FDA disputed this claim in its presentation, saying Capricor was advised to not change the endpoint.Following the CRL in July 2025, Capricor requested a Type A meeting with the FDA where the biotech asked to change the Phase 3 trial’s primary endpoint to LVEF in order to “reposition HOPE-3 to support a BLA in cardiomyopathy,” Marbán said. The FDA said no.“If the agency wanted us to only focus on cardiomyopathy, why did they insist that we keep the primary efficacy endpoint in HOPE-3 as upper limb function?” she asked.On this point, the committee members questioned the use of LVEF, which has “too many questions with the sensitivity and choice of data,” according to Christopher Coffey, director of Clinical Trials Statistical Data and the Data Management Center at the University of Iowa College of Public Health, who voted against the cell therapy.

Upper limb, meanwhile, “is a little more favorable, but I’m not convinced that it works.”Marbán expressed frustration in the agency’s recent upheaval, which has included massive layoffs and leadership changes.“We recognize that the agency has undergone significant change over the past year, and that some of the institutional knowledge of those interactions may have been lost along the way,” she said. “But we are now fighting for the life of this therapeutic on the basis of a timeline that has been misconstrued.”Just after the meeting got underway on Wednesday, Capricor announced the publication of data from HOPE-3 in The Lancet showing that treatment with deramiocel slowed upper limb decline by 54% vs. placebo and led to a “clinically meaningful cardiac benefit.”“The manuscript underwent independent expert peer review, providing external validation of the trial’s design, statistical methodology and findings,” Capricor said in a Wednesday morning press release.Marbán added that the company’s Phase 1 and 2 trials of deramiocel were also published in “highly regarded academic journals.” Results from the Phase 1/2 HOPE-Duchenne study were published in The American Academy of Neurology Journal in 2019, followed by the Phase 2 HOPE-2 trial in The Lancet in 2022.“The most important takeaway from our decade of clinical work in Duchenne muscular dystrophy is that every study points in the same positive direction across both skeletal and cardiac function,” Marbán concluded.

“Lightning does not typically strike three times in the same place.”Correction (July 30): The previous headline of this piece said that FDA reviewers voted against deramiocel, when, in fact, it was the advisory committee. BioSpace regrets the error. Twitter LinkedIn Facebook Email Print Duchenne muscular dystrophy Rare diseases FDA Regulatory Capricor Therapeutics Heather McKenzie Heather McKenzie is senior editor at BioSpace.

You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.