FDA Issues CRL to Deramiocel for Treating Cardiomyopathy Secondary to DMD

The US Food and Drug Administration (FDA) delivered a Complete Response Letter (CRL) to Capricor Therapeutics’ Biologics License Application (BLA) for deramiocel, a lead candidate for the treatment of cardiomyopathy associated with Duchenne muscular dystrophy (DMD).1

Announced by Capricor on July 11, 2025, the CRL stated that the FDA was incapable of approving the BLA as it did not meet the statutory requirement for substantial evidence of effectiveness and the need for additional clinical data. The FDA indicated outstanding items in the Chemistry, Manufacturing, and Controls (CMC) section of the application. Capricor stated their belief that these issues were addressed in prior communications with the FDA, but the materials were not reviewed by the Agency due to the timing of the CRL issuance.1

“We are surprised by this decision by the FDA,” stated Linda Marban, PhD, chief executive officer of Capricor. “We have followed their guidance throughout the process. Prior to the CRL, the review had advanced without major issues, including a successful pre-licensure inspection and completion of the mid-cycle review.”1

In the press release, Capricor announced plans to resubmit the BLA in Q3 2025, accompanied by additional data from the randomized, multi-center, placebo-controlled, double-blind HOPE-3 trial, which will provide further evidence of effectiveness from a well-controlled study.1

As described in the release, the FDA confirmed it will restart the review clock upon resubmission. In addition, the Agency offered the Company the opportunity to request a Type A meeting to discuss the path forward, and Capricor indicated plans to engage further with the FDA to determine the appropriate next steps.1

Deramiocel is constructed from allogeneic cardiosphere-derived cells (CDCs), a rare population of cardiac cells that exert potent immunomodulatory and anti-fibrotic actions in preserving cardiac and skeletal muscle function in dystrophopathies such as DMD. CDCs secrete exosomes, which target macrophages to alter their expression away from pro-inflammatory phenotypes.1

Deramiocel was granted Priority Review in March 2025 and assigned an initial Prescription Drug User Fee Act (PDUFA) action date of August 31, 2025. At the time, Capricor’s BLA submission was supported by data from the Phase 2 HOPE-2 and HOPE-2 open-label extension trials, both of which highlighted deramiocel’s ability to improve cardiac measures compared to placebo; specifically, that it reduced left ventricular ejection fraction, indexed left ventricular end-systlolic and end-diolastic volumes.2

The ongoing HOPE-3 trial, investigating ambulatory and non-ambulatory boys randomized in a 1:1 ratio to either deramiocel or placebo, is expected to produce topline results by the third quarter of 2025. Capricor plans to supplement a BLA resubmission with these findings.1,3

“We believe these data, if positive, along with our existing long-term clinical results showing cardiac stabilization, preservation of skeletal muscle function, and a consistent safety profile, could support efforts to resolve the questions raised by the FDA for the treatment of cardiomyopathy associated with DMD,” Marban said. “While this was an unexpected decision by the FDA, we remain committed to the DMD community to get deramiocel through the approval process.”1

References

1. Capricor Therapeutics Provides Regulatory Update on Deramiocel BLA for Duchenne Muscular Dystrophy. Capricor Therapeutics, Inc. July 11, 2025. Accessed July 11, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/319/capricor-therapeutics-provides-regulatory-update-on

2. Iapoce C. FDA Grants Priority Review to Deramiocel for DMD Cardiomyopathy. HCPLive. March 10, 2025. Accessed July 11, 2025. https://www.hcplive.com/view/fda-grants-priority-review-to-deramiocel-for-dmd-cardiomyopathy

3. Capricor Inc. A Study of Deramiocel (CAP-1002) in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy (HOPE-3). ClinicalTrials.gov identifier: NCT05126758. Updated June 13, 2025. Accessed July 11, 2025. https://clinicaltrials.gov/study/NCT05126758