Capricor Therapeutics announced that its cell therapy candidate, deramiocel, has achieved both primary and secondary endpoints in a pivotal Phase III trial for Duchenne muscular dystrophy (DMD) cardiomyopathy. This comes after the U.S. Food and Drug Administration (FDA) rejected the company’s initial application in July.
In the HOPE-3 trial, deramiocel showed statistically significant improvement in upper-limb function, which was the study’s main goal. The treatment also slowed the decline of cardiac function as measured by left ventricular ejection fraction, meeting a key secondary measure.
According to Capricor’s statement, deramiocel led to a 54% reduction in skeletal muscle disease progression. Craig McDonald, principal investigator and professor at UC Davis Health, described this outcome as “extraordinary in Duchenne.” The therapy also slowed cardiac function decline by 91% compared to placebo.
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.”
Capricor CEO Linda Marbán told analysts: “This call this morning represents the culmination of 20 years of work. 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 new results, Capricor plans to submit additional data as part of its response to an FDA complete response letter issued earlier this year.
Marbán said: “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.”
The path toward potential approval has been complicated for Capricor and deramiocel. In July, regulators said Capricor’s submission did not meet requirements for substantial evidence of effectiveness. Marbán described this as unexpected given previous positive interactions with FDA staff.
Deramiocel has been affected by recent changes within FDA leadership and communication processes. In June, Vinay Prasad from FDA’s Center for Biologics Evaluation and Research canceled an advisory committee meeting related to deramiocel without prior notice on official channels. Marbán said: “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,” she told BioSpace in August. “I couldn’t make an official statement.”
Reports indicate that disagreements over how deramiocel should be handled contributed to administrative changes at FDA earlier this year involving Nicole Verdun and Rachael Anatol—two senior officials who were placed on leave following internal disputes about Capricor's file.
Marbán emphasized that while much research focuses on treating muscular symptoms of DMD, it is often heart complications that prove fatal for patients over time.
“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.”
