The Food and Drug Administration has disagreed with Capricor Therapeutics’ claim that its Duchenne muscular dystrophy cell therapy, deramiocel, met the primary endpoints in a Phase 3 trial, according to briefing documents released ahead of an advisory committee meeting scheduled for July 29.
In December last year, Capricor reported that deramiocel achieved both the primary and secondary endpoints in the pivotal HOPE-3 trial. However, FDA reviewers wrote that the study "did not meet its pre-specified primary and secondary efficacy endpoints, showing no statistically significant difference between deramiocel and placebo at 12 months." The agency noted changes were made to the statistical analysis plan after completion of the randomized portion of the trial and during its open-label extension period. These included modifications to endpoint definitions, analytical methods, and data imputation strategies for certain intercurrent events.
The FDA also raised concerns about blinding effectiveness in HOPE-3 due to a distinctive adverse event profile: hypersensitivity reactions occurred in 42% of patients treated with deramiocel compared to 15% receiving placebo. Reviewers said this could allow treatment assignment to be inferred even under formal blinding conditions. Following publication of these findings on Monday morning, Capricor shares fell more than 65% to $6.53 per share.
Capricor CEO Linda Marbán responded by saying, “It’s been very disconcerting to us... We take great issue with how FDA analyzed the data using [SAP version 1.1].” She added that this particular statistical analysis plan was only provided when requested by FDA after Capricor’s biologics license application resubmission. “So we were blown away that they would use something that was not even intended by us ever to be used,” Marbán said. She further stated that attempts have been made to discuss these concerns directly with FDA, but "they are refusing to meet with us.”
Capricor's first application for regulatory approval was rejected by FDA last July after a planned advisory committee meeting was canceled without prior notification from the agency. Marbán said last month she had been surprised when informed an advisory committee would be held on July 29 regarding their resubmitted application before an August action date: “We really thought that it’s a very clean data set... We have not gotten any issues that they want to discuss.”
Marbán issued a statement late Monday morning asserting, “Capricor has engaged fully and transparently with the FDA throughout the review process for our biologics license application for Deramiocel and has been responsive to every request from the FDA.” She emphasized results are governed by SAP version 3.0 finalized prior to unblinding and criticized reliance on earlier draft versions in post-hoc analyses presented by FDA reviewers. "The results from HOPE-3 demonstrate a statistically significant benefit on the primary endpoint [upper limb performance], with supportive benefits in cardiac function," Marbán said.
Looking ahead, Marbán expressed confidence: “I fundamentally believe that the adcomm will be able to see through the statistical analysis plans and not turn this into something mathematical, but actually look at the treatment effect that has been consistent [across Capricor’s trials].” The advisory committee meeting is set for July 29.
