FDA Peels Back CRL on Capricor's DMD Cardiomyopathy Cell Therapy Deramiocel

This article was originally published on our sister site, NeurologyLive®.

The FDA has lifted the complete response letter (CRL) previously issued for Capricor Therapeutics’ biologics license application (BLA) seeking approval of deramiocel, an investigational allogeneic cardiosphere-derived cell therapy being developed to treat cardiomyopathy associated with Duchenne muscular dystrophy (DMD).¹

Following the move, the application has been classified as a Class 2 resubmission, and the agency has established a new Prescription Drug User Fee Act (PDUFA) target action date of August 22, 2026. The FDA’s decision to resume review of the BLA was based on additional data and supporting materials submitted from the ongoing phase 3 HOPE-3 trial (NCT05126758). These HOPE-3 data were not included in the original rolling BLA package, which was finalized in January 2025 and relied primarily on findings from the HOPE-2 trial (NCT03406780) and its open-label extension study (HOPE-2-OLE; NCT04428476). Outcomes from those studies were analyzed in comparison with an FDA-funded natural history dataset.²

Capricor stated that, if deramiocel ultimately receives approval, the resubmitted BLA could qualify the company for a Priority Review Voucher. The company also indicated that the FDA has not raised any new concerns regarding the updated application as part of the ongoing review process.

“We submitted our documentation in response to the CRL that we got from FDA last summer,” Linda Marbán, PhD, the chief executive officer of Capricor, told CGTLive® during an in-person interview at the 2026 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 8-11 in Orlando, Florida. “They wanted a randomized, double-blind, placebo-controlled trial to look specifically at the cardiomyopathy associated with Duchenne, which is what our BLA was for. We were able to give them that in the HOPE-3 clinical data. We had asked them to switch the primary efficacy end point to ejection fraction (EF), a measure of how the heart meets the needs of the body. Because the open BLA was for cardiomyopathy, they didn't want to switch the primary efficacy end point and so they said to submit the data as it is.”

The CRL was issued to Capricor in July 2025.³ At the time, the FDA stated that the statutory requirement for “substantial evidence of effectiveness” was not met and that more clinical data would be needed. Furthermore, the FDA also drew attention to outstanding parts of the BLA’s Chemistry, Manufacturing, and Controls (CMC) section, that were not reviewed by the agency because of the CRL’s timing; although, Capricor noted at the time that most of these CMC items had been addressed previously in its interactions with the FDA.

“[In HOPE-3], we hit both the primary of performance of the upper limb and the key secondary of EF,” Marban continued in the interview. “Now, we're looking forward to the PDUFA date [and] we anticipate labeling negotiations to happen. Prior to that, we'll update the community on what the label indication will be. We're going to try and get not only the cardiomyopathy label, but also a skeletal muscle function or DMD label because we had such robust results in that aspect of the trial, as well.”

Later in 2025, the FDA published the CRL publicly on its website.⁴ In September 2025, Capricor published its own full response to the CRL. Capricor stated that it was not notified in advance by the FDA that the latter would be publishing the CRL publicly on its website. Furthermore, the FDA did not publish Capricor’s response to the CRL, which, according to the company, provides clarifications on the feedback received and insight on its proposed plans to address remaining issues.

“Transparency is vital in regulatory communications, especially when patients are waiting for therapies with the potential to alter the course of devastating diseases such as DMD...” Marbán said in a September 2025 press release.⁴ “While we respect the FDA’s process, we believe it is important that the public has visibility into both the CRL and our detailed written response submitted to the agency.”

REFERENCES
1. Capricor Therapeutics announces establishment of new PDUFA date for Deramiocel BLA. News release. Capricor Therapeutics. March 10, 2026. Accessed March 10, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/338/capricor-therapeutics-announces-establishment-of-new-pdufa
2. Capricor Therapeutics Completes Submission of Biologics License Application to the U.S. FDA for Deramiocel for the Treatment of Duchenne Muscular Dystrophy. News release. Capricor Therapeutics. January 2, 2025. Accessed March 10, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/303/capricor-therapeutics-completes-submission-of-biologics
3. Capricor Therapeutics provides regulatory update on Deramiocel BLA for Duchenne muscular dystrophy. News release. Capricor Therapeutics. July 11, 2025. Accessed March 10, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/319/capricor-therapeutics-provides-regulatory-update-on
4. Capricor Therapeutics responds to FDA posting of complete response letter (CRL) for deramiocel. News release. Capricor Therapeutics. September 9, 2025. Accessed March 10, 2026. https://www.capricor.com/investors/news-events/press-releases/detail/325/capricor-therapeutics-responds-to-fda-posting-of-complete