The FDA has granted a three-month extension for Capricor Therapeutics’ Duchenne muscular dystrophy hopeful deramiocel in order to review additional data and consider a refined indication. The new target action date for the therapy is November 22.
After the PDUFA date for Capricor Therapeutics’ Duchenne muscular dystrophy cell therapy came and went this weekend without any word, the biotech announced a three-month extension granted by the FDA to review additional data supporting a refined indication.
After a contentious advisory committee meeting late last month—during which advisers voted 9-3 against recommending approval for deramiocel—Capricor submitted an amendment to its biological license application (BLA) that includes 24-month open-label extension data from the pivotal Phase 3 HOPE-3 study. The amendment also includes a request that the FDA review both existing and new data “in support of a refined proposed indication focused on upper limb function,” which was the study’s primary endpoint.
The FDA’s original action date for deramiocel was Aug. 22. The new PDUFA has been set for Nov. 22, as the agency has classified the submission as a “major amendment.” Capricor’s stock was up as much as 16% Monday morning. At the time of publication, the stock was worth $7.05 per share.
Deramiocel has also been proposed to treat Duchenne muscular dystrophy (DMD) cardiomyopathy. In fact, Capricor CEO Linda Marbán previously told BioSpace that the company requested in a pre-BLA meeting last August to switch the primary efficacy endpoint of the HOPE-3 trial to left ventricular ejection fraction (LVEF) from change from baseline in upper limb function. The biotech subsequently submitted a protocol amendment to designate LVEF as the primary efficacy endpoint for HOPE-3, with performance of the upper limb as a pre-specified secondary endpoint.
No such change was ultimately made, but at last month’s adcomm, FDA advisers and reviewers spent a substantial amount of the adcomm on this cardiac-related secondary endpoint. The committee members called the data around the secondary endpoint “very fragile,” and ultimately voted 9-3 against approval based on the therapy’s efficacy in DMD cardiomyopathy.
Marbán argued that this focus was flawed. Not only was LVEF a secondary endpoint, but it was calculated across the full DMD population rather than in patients with established cardiomyopathy—the population the proposed indication addresses. Capricor is now looking to bring the focus back to upper limb function as it looks ahead to its new PDUFA date.
“With an additional year of follow-up from HOPE-3, we now have one of the most extensive clinical datasets evaluating upper limb function in Duchenne,” Capricor CEO Linda Marbán said in a statement on Monday. “HOPE-3 met its primary endpoint, demonstrating a statistically significant benefit in upper limb function, and we believe the additional open-label data and further analyses included in the amendment strengthen the evidence supporting a refined proposed indication.”
“We appreciate the FDA’s continued engagement and look forward to working constructively with the agency as it completes its review,” the CEO added.
Capricor shareholder Kaos Capital objected to plans recently announced by the biotech to halt all other pipeline work until the biotech receives “further regulatory clarity” on deramiocel.
“We are shareholders because we believe deramiocel may still have meaningful value for patients and because we recognize the potential inherent in Capricor’s cell-therapy and exosome capabilities,” the firm wrote in an August 21 letter to other shareholders. “But conviction in a lead program is not a license for a Board to concentrate all of a public company’s capital, risk, and future in a single regulatory outcome.”
