Capricor Therapeutics’ cell therapy for Duchenne muscular dystrophy has come up short at the FDA, with the regulator rejecting the biotech’s application seeking regulatory approval for what the company hoped would become the first treatment developed specifically for the cardiovascular complications of this rare disease.
The FDA’s complete response letter stated the application for the therapy, named Deramiocel, lacks substantial evidence of effectiveness and needs additional clinical data, San Diego-based Capricor said Friday. The submission was based on data from a placebo-controlled Phase 2 test. A larger placebo-controlled Phase 3 study is ongoing; preliminary results are expected later in the current quarter. Capricor CEO Linda Marbán said the company plans to resubmit the application for the therapy with data from the Phase 3 study to provide the additional evidence the FDA requires.
“We believe these data, if positive, along with our existing long-term clinical results showing cardiac stabilization, preservation of skeletal muscle function, and a consistent safety profile, could support efforts to resolve the questions raised by the FDA for the treatment of cardiomyopathy associated with [Duchenne muscular dystrophy],” Marbán said in a prepared statement.
Duchenne is an inherited disorder that leads to deficiency of dystrophin, a key muscle protein. While the disease initially manifests as progressively worsening skeletal muscle weakness, it also affects cardiac muscle, leading to cardiomyopathy and heart failure. Capricor’s Deramiocel is an off-the-shelf therapy made from donor cardiac tissue. Cardiospheres, a rare type of cardiac cell, are isolated from the donor samples. Administered to a Duchenne patient, these cells secrete tiny vesicles called exosomes that target macrophages, a type of immune cell. Capricor says these cells bring patients therapeutic effects, including counteracting inflammation and fibrosis in cardiac tissue.
In March, the FDA accepted Capricor’s biologics license application for Deramiocel under priority review, setting an Aug. 31 target date for a regulatory decision. But agency leadership has changed since then. Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research (CBER), abruptly left the FDA in April after reportedly clashing with Health and Human Services Secretary Robert F. Kennedy Jr. Marks was succeeded by Vinay Prasad, a hematologist-oncologist who has been critical of some accelerated FDA approvals based on thinner bodies of evidence, including the approvals of some Duchenne therapies.
In May, Capricor said the FDA would convene an advisory committee meeting to discuss the cell therapy. But in late June, the FDA informed Capricor that this advisory meeting was no longer needed. That announcement came days after Nicole Verdun, director of the Office of Therapeutic Products within CBER, was placed on administrative leave. Prasad was skeptical of the Capricor cell therapy and unilaterally canceled the advisory meeting, the health news site Stat reported at the time, citing an unnamed source familiar with the matter.
In Capricor’s Friday announcement, Marbán characterized the FDA’s decision on Deramiocel as a surprise. Prior to the complete response letter, the review of Deramiocel proceeded without major issues, she said. The letter also referenced matters in the chemistry, manufacturing, and controls section of the application. The company believes it has addressed these matters but those responses have not been formally reviewed by the agency due to the complete response letter. Capricor plans to request a meeting with the FDA to discuss the next steps.
Investors frowned on the FDA rejection of Deramiocel. Capricor’s stock price opened Friday at $6.99, down 38.6% from Thursday’s closing price.
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