After an FDA advisory committee voted 9-3 on Wednesday against recommending Capricor Therapeutics’ Duchenne muscular dystrophy cardiomyopathy drug for approval, stakeholders allege an “ulterior motive” and “biased intentions.”
Capricor Therapeutics’ share value nosedived after an FDA advisory committee voted against recommending the biotech’s candidate for Duchenne muscular dystrophy cardiomyopathy. The adcomm was contentious, and CEO Linda Marbán is not ruling out legal action.
When asked about taking the matter to the courts in an interview with BioSpace on Thursday, Marbán responded: “I don’t know.”
“I like to collaborate. I’m a consensus builder. My number one goal is to meet with the agency and figure out a path forward that works for everybody,” she continued. “If they really dig their heels in and they say there’s no path forward for this therapeutic, we’ll explore strategic options for the therapy. Pull it off of the Duchenne space, and yeah, pursue legal action.”
The FDA did not respond to BioSpace’’s question about whether the agency was concerned about a legal challenge.
On Wednesday, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted 9-3 that Capricor’s cell therapy, deramiocel, was not effective in its target indication. While the FDA does not have to follow the committee’s recommendation and has not yet issued a decision, it is unusual for the agency to act counter to the outcome of an adcomm’s vote.
Capricor’s shares have fallen nearly 80% over the past five days, though the stock did rebound to close at $4.19 on Thursday, compared to $6.69 prior to the meeting.
The FDA Crockpot
For Marbán, it appears the cards were stacked against the therapy.
“It was very clear from the voting question and sort of how [FDA] pitched it with stat plan 1.1 that they seem to have some type of ulterior motive in trying to take this therapeutic down, and I can’t figure out why,” she said Thursday.
Marbán was referring to statistical analysis plan (SAP) 1.1—a draft that Capricor never intended to be considered in the approval application. The agency used this version, rather than the most recently submitted SAP 3.0, as a “benchmark” because it was the plan in place when the study initiated, FDA biostatistical analyst Tingting Zhou said during her presentation.
When asked if this was normal practice, Marbán said it is not. “There’s always tweaks made. There’s always changes made, up to the very end of a trial until unblinding occurs,” she said. “It’s standard industry practice.”
SAP 1.1 was an unsigned, incomplete internal draft, Marbán said, which became obsolete with the addition of the Phase 3 HOPE-3 trial’s cohort B and did not include content specifically requested by the FDA.
“They said it’s a signed draft. It wasn’t a signed document. It never was. We provided it as a courtesy post BLA resubmission when they asked for all drafts of the SAP,” she said, adding: “We’ll use this if we ever have to legally.”
The FDA on Thursday disputed the singular focus on SAP 1.1. In an email to BioSpace, a spokesperson said the agency’s briefing document and presentations during the meeting “included a thorough evaluation of Capricor’s data in the context of several versions of their statistical analysis plans, from the version drafted at the start of the trial to the final version 3.0, which was created by Capricor one day prior to unblinding.”
But the focus on SAP 1.1 was critical, Marbán argued, as its benchmark p value—a measurement of how compatible observed data are with the null hypothesis—did not yield significance when applied to the study’s primary outcome when FDA applied this version in its analysis of the data.
“Their p value using 1.1 didn’t take into account any of the specifics of intercurrent events, how to manage missing data, any of that,” Marbán continued. “They just kind of threw it all together in a crockpot and hoped for dinner.”
The rest of the SAPs—there were several—showed statistical significance, she said. “That’s why I keep hoping that there’s a path forward.”
The lack of significance in SAP 1.1 was included in a publication of the HOPE-3 trial in The Lancet on Wednesday, and garnered copious discussion at the adcomm meeting. The results in the publication—which hit the wires minutes after the meeting began—were otherwise positive, showing that treatment with deramiocel slowed upper limb decline by 54% versus placebo and led to a “clinically meaningful cardiac benefit,” according to a Capricor press release.
From the patients
Marbán isn’t alone in her concerns about how the adcomm meeting played out.
“There were some really disingenuous things that were done to put together the analysis that they came up with,” said Mindy Leffler, a patient advocate and consultant who testified during Wednesday’s meeting along with her son, Aidan Leffler, who has DMD and took part in the Phase 2 HOPE-2 trial.
Leffler told BioSpace that, according to the FDA’s presentation, the HOPE-3 study was powered in SAP 1.1 to detect a 1.5-point difference in PUL v2.0—a scale designed to measure upper limb performance—as compared to placebo. However, she said, this analysis, which only included one of the two study cohorts, showed a lower separation than what was seen when the second cohort was included as laid out in a later version of the SAP—at which point the study was powered to detect a 1.1 point difference.
“That creates the optics that [deramiocel] didn’t reach the degree of separation that the study was powered to detect,” Leffler said. “To me, that is evidence of biased intentions.”
As for a potential path forward for the cell therapy, Marbán noted that Capricor has a few weeks left before deramiocel’s Aug. 22 action date to “see if there’s a strategy to move it forward” with the FDA. Otherwise, Capricor may look beyond the U.S.
“I think there’s some appetite on my board to go outside the U.S., go to Europe and finish the work there and get approval there,” she added. “Historically, if you look at other therapeutics, that pathway is not usually fabulous in terms of coming back to the U.S.”
Tougher terrain for Duchenne?
Last month, Marban suggested to BioSpace that one possible reason the FDA may have convened Thursday’s adcomm is the recent regulatory friction in the DMD space more broadly.
Controversy unspooled last July when the agency temporarily requested that Sarepta Therapeutics halt shipments of its gene therapy Elevidys following the deaths of two nonambulatory patients with the neuromuscular disease. After weeks of back-and-forth, Elevidys remains on the market for patients who are able to walk.
“There’s been so many issues around Duchenne and treatment for Duchenne and Sarepta, maybe they’re being extra careful,” Marbán said prior to the planned adcomm.
However, at least one analyst doesn’t see a broader impact stemming from the vote on deramiocel.
In a note to investors on Wednesday, Oppenheimer analysts said they “see no readthrough from [Capricor’s] adcom vote” to other companies in the space, which include Sarepta, Precision BioSciences, Dyne Therapeutics, Satellos Bioscience and Entrada Therapeutics.
“We believe the panel/public continue to see high unmet need in DMD and there could be potential regulatory flexibility that could support multiple, potentially combinable DMD therapies,” the analysts said, adding that, with the exception of Sarepta’s Elevidys, none of these companies have used PUL v2.0 as a primary functional endpoint.
Indeed, the panelists were conflicted on Wednesday, given the high unmet need in DMD-associated cardiomyopathy—the leading cause of death for these patients. While Patient Advocate Debra Dunn voted yes, even she 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.”
Notably, Sarepta is currently awaiting an FDA decision regarding traditional approval of its exon skippers Amondys 45 and Vyondys 53, both of which failed a confirmatory trial in November 2025. The two DMD drugs are already on the market under the FDA’s accelerated approval pathway. Marbán noted that NS Pharma’s Viltepso also failed a confirmatory study in DMD in May 2024, yet it remains on the market.
“Every confirmatory trial has failed, and everybody else got accelerated approval,” Marbán said. “There’s something really wrong here.”
