Capricor Therapeutics’ experimental stem cell treatment for Duchenne muscular dystrophy failed to meet the primary and secondary objectives of a Phase 3 clinical trial, according to review documents released by the Food and Drug Administration. The regulatory setback arrives ahead of an upcoming advisory committee meeting to evaluate the therapy, designated deramiocel, for the fatal childhood muscle-wasting disease.
FDA Review Finds Trial Falls Short of Efficacy Goals
According to FDA briefing documents published ahead of an agency advisory panel hearing, regulators determined that Capricor’s late-stage study did not achieve statistical significance. The evaluation compared deramiocel against a placebo across pre-specified endpoints measuring upper-arm skeletal muscle function and cardiac performance.
The federal agency stated that its own examination revealed only small and variable changes in measures of upper limb function and cardiac imaging parameters. These observed variations failed to reach statistical significance and presented challenges for clinical interpretation, according to the regulatory review.
Furthermore, regulators highlighted safety considerations tied to the investigational cell therapy, noting documented occurrences of infusion-related reactions and anaphylaxis. Under statutory guidelines cited by the agency, a drug must demonstrate convincing and substantial clinical evidence of effectiveness where observed benefits outweigh potential risks.
Dispute Over Statistical Analysis Plan Modifications
A central point of contention in the regulatory review involves alterations made to the trial’s statistical analysis plan. The FDA stated that Capricor made a series of modifications to the analysis blueprint after the clinical study was completed.
Regulators noted that revising measurement plans post-study introduces the possibility of generating positive outcomes that were not apparent under the trial’s original design. Additionally, the company’s submission to the agency incorporated analyses that were absent from any finalized statistical analysis plan.
Capricor Chief Executive Officer Linda Marban pushed back against the agency’s characterization during an interview. Marban stated that the company was completely surprised by the assertions, maintaining that regulators relied on an early draft of the analysis plan containing Post-it notes that was never fully completed.
According to Marban, the updated statistical analysis plan was submitted at the direct request of the FDA before the study data were unblinded. She asserted that the company has been unable to secure substantive feedback from the agency.
Advisory Committee Evaluation and Regulatory Precedent
Independent advisors to the FDA are scheduled to review and cast votes regarding the efficacy data for deramiocel during a public hearing. The upcoming session is anticipated to draw extensive participation from patient advocates, families, and clinical investigators.
A group of trial investigators submitted a letter to the FDA urging regulators to consider a broad labeling indication for the treatment. Patient communities have maintained strong advocacy for the therapy, emphasizing the scarcity of available options for teenagers and young men who have lost ambulation and face progressive heart failure.
The current evaluation follows earlier regulatory hurdles. The FDA previously declined a marketing application for deramiocel submitted on the basis of a smaller Phase 2 study.
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