New trial results highlight gains in arm and heart function for DMD
Experimental therapy deramiocel slowed disease progression in Phase 3 study
In the Phase 3 HOPE-3 clinical trial, the experimental cell therapy deramiocel outperformed a placebo at improving arm function and heart health in people with Duchenne muscular dystrophy (DMD), according to top-line results announced by its developer, Capricor Therapeutics.
Capricor has said it plans to use the HOPE-3 data as a basis to resubmit its application for U.S. Food and Drug Administration (FDA) approval of deramiocel. The company previously applied to the FDA seeking approval based on Phase 2 study results, but the FDA rejected that application earlier this year, saying more data were needed to show the therapy was effective.
“HOPE-3 delivered strong and definitive evidence that Deramiocel can meaningfully improve the course of Duchenne muscular dystrophy, demonstrating statistically significant improvements in both skeletal and cardiac function,” Linda Marbán, PhD, CEO of Capricor, said in a company press release. Marbán said the Phase 2 and Phase 3 data “position us to address the clinical issues in the [FDA’s rejection] received earlier this year, consistent with prior FDA guidance that HOPE-3 results should be sufficient to support regulatory approval.”
How deramiocel aims to protect muscles damaged by Duchenne
DMD is a genetic disease that causes muscles to accumulate damage over time. It affects the skeletal muscles used for movement, as well as heart muscle, which can lead to serious heart problems such as cardiomyopathy. Deramiocel, formerly known as CAP-1002, is a therapy containing immature heart cells that release signaling molecules to help support muscle repair.
The Phase 2 HOPE-2 trial (NCT03406780) tested deramiocel against a placebo in 20 people with DMD. Results indicated the therapy improved heart and arm function, with signs of improvement relative to the typical course of DMD seen over four years of follow-up in an open-label extension study (NCT04428476).
A nearly 54 percent slowing of skeletal muscle disease progression is extraordinary in Duchenne and directly linked to maintaining independence and quality of life in the most severely affected patients with greatest unmet need.
Building on those Phase 2 findings, Capricor launched the Phase 3 HOPE-3 trial (NCT05126758). The study enrolled 106 boys and men with DMD, ages 10 and older, who were randomly assigned to receive either deramiocel or a placebo every three months. Most participants were unable to walk, and more than three-quarters had a clinical diagnosis of cardiomyopathy.
Participants were then followed for one year. The main goal was to measure changes in scores on the Performance of the Upper Limb test, version 2 (PUL 2.0), a standardized tool used to track arm and hand function. In DMD, PUL 2.0 scores usually decline over time. In HOPE-3, deramiocel slowed this decline by an average of 54% compared with placebo.
“A nearly 54 percent slowing of skeletal muscle disease progression is extraordinary in Duchenne and directly linked to maintaining independence and quality of life in the most severely affected patients with greatest unmet need,” said Craig McDonald, MD, an investigator on HOPE-3 at the University of California Davis. “The preservation of function reflected in PUL v2.0 translates into real, practical benefits for boys and young men living with this disease.”
Therapy also showed strong signals of benefit for heart function
A key secondary goal was to evaluate left ventricular ejection fraction (LVEF), a measure of how well the heart pumps blood to the body. Results showed that deramiocel slowed the decline in LVEF by 91% compared with placebo.
“The cardiac findings from HOPE-3 represent a significant advance in the management of Duchenne muscular dystrophy cardiomyopathy,” said Jonathan Soslow, MD, a professor at Vanderbilt University Medical Center. “Cardiomyopathy is the leading cause of mortality in Duchenne, and stabilizing cardiac function has remained a major unmet need. The statistically and clinically significant preservation of left ventricular ejection fraction in patients treated with Deramiocel observed in HOPE-3 underscores the potential of Deramiocel to address one of the most critical aspects of the disease.”
Safety data from HOPE-3 were consistent with findings from earlier studies, according to Capricor. The company did not provide additional specifics, and said detailed results will be shared at future scientific meetings and submitted for publication in a peer-reviewed journal.
“For families living with Duchenne who are looking for therapies that preserve functional ability, protect the heart and maintain independence, today’s results provide real momentum and meaningful progress, offering renewed confidence as we work to advance Deramiocel toward potential regulatory approval,” Marbán said.
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