News|Articles|September 9, 2025
In Response to FDA’s Release of Full CRL for Deramiocel, Capricor Publishes Full Response to the Agency
Author(s)Noah Stansfield
Capricor stated that it was not notified in advance by the FDA that the latter would be publishing the CRL publicly on its website.
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Following the FDA’s public release of the full complete response letter (CRL) that it issued to Capricor Therapeutics for the company’s biologics license application (BLA) for Deramiocel, an investigational allogeneic cardiosphere-derived cell therapy intended for the treatment of Duchenne muscular dystrophy (DMD) cardiomyopathy, Capricor has responded by publishing its full response to the agency.1
Capricor stated that it was not notified in advance by the FDA that the latter would be publishing the CRL publicly on its website. Furthemore, 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. As such, Capricor published its response to the CRL on its own website.
“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 Duchenne muscular dystrophy,” Linda Marbán, PhD, the chief executive officer of Capricor, said in a statement.1 “Our focus remains on working closely with the FDA to resolve the outstanding issues and to advance Deramiocel toward approval. 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. We are now awaiting the official minutes from our recent Type A meeting with the FDA review team, expected to be issued later this quarter, which will help define the next steps in our regulatory pathway. Looking ahead, we expect topline HOPE-3 data in the fourth quarter of 2025, and our discussions with the FDA have centered on how these data will inform and support the timing of our BLA resubmission.”
The BLA for Deramiocel, which completed its rolling submission in January 2025 and was accepted for review by the FDA in March 2025, was supported by results from the completed HOPE-2 clinical trial (NCT03406780) and HOPE-2’s ongoing open-label extension (OLE) study (HOPE-2-OLE; NCT04428476), with data from these studies being compared to an FDA funded natural history dataset.2,3 According to the FDA’s CRL, however, HOPE-2 did not meet its primary efficacy end point and several secondary end points.
“The HOPE-2 study failed to demonstrate efficacy for its prespecified primary efficacy endpoint, which was change from baseline to Month 12 in the mid-level (elbow) dimension of the Performance of Upper Limb version 1.2 (PUL 1.2), a neuromuscular outcome assessment,” the FDA wrote in the CRL.4 “Additionally, HOPE-2 failed to demonstrate efficacy on its prespecified secondary end points. To support your proposed indication for treatment of cardiomyopathy in patients with DMD, you have presented post hoc analyses of HOPE-2 and HOPE-2-OLE. However, as outlined below, these post hoc analyses are not sufficient to provide substantial evidence of effectiveness to support approval of deramiocel.”
In its response to the CRL, Capricor stated that the primary outcome of HOPE-2 was statistically significant “when analyzed with appropriate statistical techniques,” noting that “The primary analysis relied on an assumption of normality that was not met in the observed data and needed to be adapted to be valid.”5 In addition to responding to the FDA’s commentary on the HOPE-2 data, Capricor also noted that its planned resubmission of the BLA may include additional data from the ongoing phase 3 HOPE-3 clinical trial (NCT05126758). HOPE-3 data had not been part of the original BLA.
“At this point, Capricor has its phase 3 HOPE-3 clinical study, which has concluded enrollment of n = 104 patients with 12 months of follow-up,” the company wrote in its response to the CRL.5“Capricor intended to use the HOPE-3 program for its global expansion efforts after the BLA, but given the CRL, Capricor is considering its options to use the HOPE-3 outcomes to support address of the Clinical and Biostatistical Deficiency, although it maintains that the deficiency has been written in error.”
REFERENCES
1. Capricor Therapeutics responds to FDA posting of complete response letter (CRL) for deramiocel. News release. Capricor Therapeutics. September 9, 2025. Accessed September 9, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/325/capricor-therapeutics-responds-to-fda-posting-of-complete
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 September 9, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/303/capricor-therapeutics-completes-submission-of-biologics
3. Capricor Therapeutics announces FDA acceptance and priority review of its biologics license application for Deramiocel to treat Duchenne muscular dystrophy. News release. Capricor Therapeutics. March 4, 2025. Accessed September 9, 2025. https://www.capricor.com/investors/news-events/press-releases/detail/305/capricor-therapeutics-announces-fda-acceptance-and-priority
4. Complete Response Letter. FDA. Letter. July 9, 2025. Accessed September 9, 2025. https://download.open.fda.gov/crl/CRL_BLA125842_20250709.pdf
5. Response to 09 July 2025 Complete Response Letter. Capricor Therapeutics. Letter. Marban L and Kayo MW. July 16, 2025. Accessed September 9, 2025. https://d1io3yog0oux5.cloudfront.net/_482bc4203ea211827b4af3a98e815915/capricor/files/pages/capricor/db/2325/description/CAPR_response_letter_FINAL_%281%29.pdf
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