Capricor Therapeutics has publicly released its July response to the FDA's rejection of its Duchenne muscular dystrophy cell therapy deramiocel after the agency included deramiocel in a new batch of complete response letters (CRLs) released on Sept. 4.
The biotech said its response clarified certain points the agency had identified in the CRL and also outlined Capricor's plan to address the remaining concerns.
The FDA made waves last week by declaring it would now publicly publish rejection letters for unapproved drugs at the same time that they are issued to sponsoring companies. The agency then published 89 CRLs, including one for deramiocel, which was originally issued on July 9.
The move by the regulator follows its prior decision to release CRLs for drugs that were initially rejected but have since been approved and represents a major change in agency policy.
In a Sept. 9 release, Capricor said it was not notified in advance that the FDA was making the rejection letter public. Capricor sent its initial response to the FDA on July 16, a week after deramiocel’s rejection.
“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,” Capricor’s CEO Linda Marbán, Ph.D., said in the release. “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.”
In response to a request for comment from Fierce, the Department of Health and Human Services, which oversees FDA, pointed to a July 11 opinion piece penned by FDA Commissioner Marty Makary, M.D., outlining the agency's plan to publicly release CRLs.
The FDA’s decision to reject deramiocel centered on supposed deficiencies with Capricor’s phase 2 DMD trial and open-label extension studying cardiomyopathy secondary to DMD, according to the CRL.
The FDA wrote that the HOPE-2 trial “failed to demonstrate efficacy for its prespecified primary efficacy endpoint,” which was a change from baseline in a measure of neuromuscular function. In its response, Capricor said this endpoint was actually met.
“The primary outcome was statistically significant when analyzed with appropriate statistical techniques,” the biotech wrote July 16. This involved adjusting the analysis to account for the fact that the data did not meet all the assumptions required to use a t-test, a common test of statistical significance.
When the data was analyzed using what Capricor called "a more appropriate technique"—a non-parametric test—the endpoint was met with a p-value of 0.014, which is statistically significant.
Capricor’s application also sought approval for use of deramiocel to treat DMD-associated cardiomyopathy, a condition where the heart has trouble pumping enough blood, which is common in patients with DMD.
In its CRL, the FDA declared that the data submitted to support a cardio approval include “50 secondary and exploratory endpoints,” which “were not prespecified for hypothesis testing” and had no controls in place to account for the potential of false positives.
While acknowledging that adjustment for potential false positives was not done, Capricor in general expressed bafflement at the FDA’s concerns, saying that all of the endpoints were prespecified for hypothesis testing and that the company’s plans had been discussed extensively with the agency prior to the biologics license application (BLA) submission.
“Capricor has prepared its BLA based on feedback from FDA’s cardiology review team and with full transparency of its intentions,” the San Diego-based company wrote in its July 16 response to the CRL. “It is difficult to understand the massive change in the agency’s feedback provided in the CRL, when the initial plan to use the HOPE-2 and HOPE-2-OLE as the clinical basis for the BLA was set into motion with FDA’s agreement just under one year ago.”
The FDA’s Center for Biologics Evaluation and Research has zeroed in on companies seeking approvals for cell and gene therapies, especially for rare diseases, under leader Vinay Prasad, M.D. CBER has extended decision dates for Regenxbio’s Hunter syndrome gene therapy and rejected Ultragenyx’s gene therapy for Sanfilippo syndrome type A, among others, and a controversial spat with Sarepta Therapeutics over DMD gene therapy Elevidys resulted in Prasad’s temporary ouster.
Despite the rejection, Capricor is holding out hope that deramiocel will eventually be approved, CEO Marbán said in the release, with the biotech waiting for the official minutes of its recent Type A meeting with the FDA.
“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,” Marbán said.
Editor's note: This story was updated at 1:10 p.m. ET on Aug. 9 to include a statement from the Department of Health and Human Services.