— Agency says deramiocel did not meet phase III trial endpoints, contrary to reported data
by Judy George, Deputy Managing Editor, MedPage Today
July 27, 2026
• 3 min read
FDA scientists said that investigational deramiocel, a stem cell treatment for Duchenne muscular dystrophy, did not meet its primary endpoint in a phase III trial, despite data presented at the American Academy of Neurology (AAN) annual meeting to the contrary.
At the AAN meeting, researchers reported that deramiocel slowed upper limb functional decline in boys and young men with Duchenne muscular dystrophy in the phase III HOPE-3 trial. At 12 months, the mean percent change from baseline in Performance of Upper Limb 2.0 (PUL 2.0) total score was -3.86 in the deramiocel group and -8.41 in the placebo group, a difference of 4.55 (P=0.029).
However, in briefing documents presented ahead of an advisory committee meeting that will be held Wednesday, FDA staff members said that the difference in mean change in PUL 2.0 total score from baseline to month 12 was 0.66 (95% CI -0.45 to 1.77, P=0.24).
FDA staff members also said there was no statistically significant difference between deramiocel and placebo on key secondary endpoints including cardiac function. The advisory committee meeting documents prepared by deramiocel’s developer, Capricor Therapeutics, mirrored the AAN presentation.
The differences appear to lie in the statistical analysis plan (SAP) used in the study. The FDA analysis used SAP version 1.1, which the agency said was prespecified. The plan used in Capricor’s analysis was a later version.
The FDA claimed the later version of the statistical plan was used after the study was unblinded. If true, this could signal a concern that a company might be trying to produce a favorable trial result that was not achieved under the original plan.
The 1.1 version of the plan was not prespecified, Capricor maintained. “SAP version 1.1 was not signed,” CEO Linda Marbán, PhD, said in an interview with MedPage Today. “Our results are governed by the final analysis plan, SAP version 3.0, which was finalized and signed before unblinding.”
Duchenne muscular dystrophy is caused by mutations in the DMD gene. Loss of the protein dystrophin triggers a cascade of effects, including progressive degeneration of skeletal and cardiac muscle, a pro-inflammatory and pro-fibrotic immune response that impairs repair, and a steady decline in function that can culminate in life-threatening cardiac events. The condition primarily affects males.
Deramiocel is a novel cellular therapy that demonstrated benefit on skeletal muscle function in HOPE-2 phase II trial data reported in The Lancet. The treatment consists of allogeneic cardiosphere-derived cells that have been shown to confer immunomodulatory and anti-fibrotic properties.
HOPE-2 was limited by a small sample of 20 participants. HOPE-3 assessed the efficacy and safety of deramiocel in 106 late-ambulatory and non-ambulatory male Duchenne patients, randomizing Duchenne patients at least 10 years old to quarterly infusions of deramiocel or placebo. Mild to moderate adverse events were reported in the study.
“For an investigational product to receive approval, there must be convincing and substantial clinical evidence that the product is effective in the proposed population and indication, and the observed benefits must outweigh the observed risks of the product in its intended use,” the FDA said.
The data from HOPE-3, considered together with the results of HOPE-2, “do not provide substantial evidence of effectiveness,” the agency stated. “Considering the observed safety risks, which include hypersensitivity reactions including anaphylaxis, the benefit-risk assessment for deramiocel appears unfavorable in the absence of evidence of effectiveness.”
At Wednesday’s meeting, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee will discuss whether HOPE-2 and HOPE-3 results support that deramiocel is effective in slowing the rate of cardiac function decline in Duchenne patients and treating the disease.
The committee also will vote on whether the available evidence from HOPE-3 provides substantial evidence of effectiveness of deramiocel to treat Duchenne cardiomyopathy. The FDA does not have to follow the advice of its advisory committees, but often it does.
