Christmas came early for Capricor Therapeutics, which announced Wednesday that its investigational cell therapy for Duchenne muscular dystrophy cardiomyopathy—which the FDA rejected in July—hit both the primary and second endpoints in a pivotal Phase III trial.
In the Phase III HOPE-3 trial, deramiocel showed statistically significant benefits in upper-limb function, the trial’s primary endpoint. The treatment also slowed a decline in cardiac function as measured by left ventricular ejection fraction, satisfying the key secondary endpoint.
Deramiocel elicited a 54% slowing of skeletal muscle disease progression, which principal investigator UC Davis Health professor Craig McDonald called “extraordinary in Duchenne” in Capricor’s statement on the results. Cardiac function decline was slowed by 91% vs. placebo.
In Wednesday’s announcement, McDonald noted that HOPE-3 study is the first-ever Phase III trial in a largely non-ambulatory population with DMD to successfully meet its primary endpoint.
“This call this morning represents the culmination of 20 years of work,” Capricor CEO Linda Marbán told analysts on a conference call Wednesday morning. “Through all the years of understanding the mechanism of action, trying to find the perfect way to deploy the powers of [deramiocel], we are now proud to be able to present today the data . . . that shows that the [HOPE-3 trial] has shown statistically significant improvement in both skeletal and cardiomyopathy.”
With these pivotal data in hand, Capricor plans to submit its response to the complete response letter it received from the FDA in July.
“We believe these pivotal study results, in addition to the evidence from the HOPE-2 and HOPE-2 [open label extension] studies, position us to address the clinical issues in the Complete Response Letter received earlier this year, consistent with prior FDA guidance that HOPE-3 results should be sufficient to support regulatory approval,” Marbán said in a statement.
HOPE on the Horizon?
It’s been a long road for Capricor and deramiocel. In the July CRL, the FDA said Capricor’s data package “fell short of the “statutory requirement for substantial evidence of effectiveness.”
This was a surprise to Marbán. “The complete response letter was unexpected given the trajectory of positive interactions [with the FDA],” she told investors on the company’s second quarter earnings call on August 11.
Deramiocel and Capricor have been wrapped up in the FDA’s ongoing personnel and communications dramas this year. In June, Center for Biologics Evaluation and Research Vinay Prasad canceled a previously scheduled advisory committee meeting for deramiocel. Marbán was caught off guard when she learned that the meeting was no longer listed on the Federal Register.
“Investors watch these boards all day, every day, so my phone started blowing up with ‘your adcomm has been canceled. It’s been taken down. Why?’ I had no answers to give,” Marbán told BioSpace in August. “I couldn’t make an official statement.”
Sarepta and Capricor learned of key regulatory decisions from the media and investors, and Duchenne muscular dystrophy families have turned to the news for answers. Meanwhile, the FDA insists it remains committed to notifying companies of any regulatory action before sharing information with the media or public.
August 4, 2025
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Deramiocel was also reportedly at the heart of the ouster of Nicole Verdun, the former director of the office that reviews cell and gene therapies, and her deputy, Rachael Anatol, who were pushed out of the agency in June. The two leaders were allegedly “put on administrative leave because of an argument about our file, and that Prasad wanted to CRL us and Nicole was fighting it,” Marbán recounted hearing from a STAT reporter who’d contacted her after receiving a tip from an agency insider.
While a significant amount of attention and R&D dollars are poured into developing treatments for the muscular effects of Duchenne muscular dystrophy, Marbán told BioSpace in August that cardiomyopathy is what typically takes a patient’s life.
“Duchenne takes typically between 25 and 30 years to take the life of a boy or a young man and every day during that progression of the disease, they are losing some aspect of their ability to function,” Marbán said on Wednesday’s conference call. “We hope to be able to attenuate the course of this disease with deramiocel moving forward.”
