Reviewers Question Data on Capricor's Duchenne Cardiomyopathy Cell Therapy
An FDA briefing document released ahead of a 7/29 Cellular, Tissue, and Gene Therapies Advisory Committee meeting reviewing Capricor Therapeutics’ resubmitted deramiocel for treating cardiomyopathy in male patients with Duchenne muscular dystrophy (DMD) says the company’s Phase 3 HOPE-3 study failed to meet its pre-specified primary endpoint measuring upper limb function and its key secondary endpoint evaluating changes in left ventricular ejection fraction, with no statistically significant differences observed between the therapy and placebo after 12 months.
Deramiocel is described as an investigational, first-in-class allogeneic cell therapy designed to preserve cardiac and skeletal muscle function in patients with Duchenne muscular dystrophy, a rare and fatal genetic disease marked by progressive muscle degeneration. The therapy consists of cardiosphere-derived cells that act primarily through exosomes, which are believed to modulate immune responses and reduce fibrosis, the company says.
In the briefing document, agency reviewers also raised concerns that multiple changes were made to the study's statistical analysis plan after completion of the blinded portion of the trial, including modifications to endpoint definitions, analytical methods and data handling. FDA said those changes were not prospectively agreed upon and considers the resulting analyses to be post hoc.
The agency also questioned whether the trial remained effectively blinded because hypersensitivity reactions occurred in 42% of deramiocel-treated patients compared with 15% of placebo recipients, potentially allowing investigators or participants to infer treatment assignment. Advisory committee members will be asked whether the available evidence from HOPE-3, together with earlier cardiac imaging data from HOPE-2, demonstrates that deramiocel slows the decline in cardiac function and provides substantial evidence of effectiveness for treating cardiomyopathy associated with DMD.
The resubmission follows an earlier Complete Response Letter after FDA concluded that Phase 2 data from the HOPE-2 trial and its open-label extension failed to provide substantial evidence of effectiveness or a favorable benefit-risk-risk profile.
According to the company, HOPE-3 met its primary endpoint, demonstrating a statistically significant improvement in Performance of the Upper Limb, as well as its key secondary cardiac endpoint measuring left ventricular ejection fraction. The trial also met all Type I error-controlled secondary endpoints.
Deramiocel is described as an investigational, first-in-class allogeneic cell therapy designed to preserve cardiac and skeletal muscle function in patients with Duchenne muscular dystrophy, a rare and fatal genetic disease marked by progressive muscle degeneration. The therapy consists of cardiosphere-derived cells that act primarily through exosomes, which are believed to modulate immune responses and reduce fibrosis, the company says.