Capricor plans for deramiocel resubmission after FDA rejection
Cell therapy aims to treat Duchenne muscular dystrophy-related heart disease
Capricor Therapeutics will resubmit its application for U.S. Food and Drug Administration (FDA) approval of its cell therapy deramiocel to treat Duchenne muscular dystrophy (DMD)-related heart disease, following the agency’s decision to not accept the original filing.
According to a company press release, the FDA issued a complete response letter (CRL) requesting additional clinical data, stating that the initial submission did not sufficiently demonstrate efficacy.
“We are surprised by this decision by the FDA. We have followed their guidance throughout the process,” said Linda Marbán, PhD, CEO of Capricor. “Prior to the CRL, the review had advanced without major issues, including a successful pre-licensure inspection and completion of the mid-cycle review.”
In its resubmission, “Capricor plans to submit data from the Phase 3 HOPE-3 clinical trial to provide additional evidence of effectiveness from an adequate and well-controlled study,” Marbán added.
Alongside HOPE-3 (NCT05126758) data, the company plans to include clarifications of outstanding items in the chemistry, manufacturing, and controls section of the application. Prior meetings with the FDA have addressed most of these items, according to the press release. However, the timing of the CRL means these materials weren’t reviewed.
Earlier studies of deramiocel yield positive results
In DMD, mutations in the DMD gene lead to the absence or malfunction of dystrophin, a protein that helps protect muscle cells from damage during movement. Without dystrophin, muscles progressively weaken and waste away.
The heart muscle is also affected, often leading to heart problems that include cardiomyopathy. In this condition, the heart becomes enlarged and weakened, impairing its ability to pump blood efficiently. Most individuals with DMD will eventually develop cardiomyopathy and related complications.
Deramiocel, formerly known as CAP-1002, is a cell-based therapy designed to target this cardiac involvement. It contains immature heart cells which release signaling molecules that may help reduce inflammation and scarring in the heart and support tissue repair.
The HOPE-2 clinical trial (NCT03406780) compared deramiocel to a placebo in 20 boys and young men with DMD. Participants received the medication via into-the-vein, or intravenous, doses every three months for a year. Results have shown improved heart and arm function in treated participants compared to the control group.
Four year follow-up data from the HOPE 2 open-label extension study (NCT04428476) demonstrated stability in left ventricular ejection fraction (LVEF), which measures how well the heart pumps oxygen-rich blood throughout the body. Participants who started the study with LVEF of 45% or greater saw less decline in heart function, indicating a potential protective effect with early treatment.
The Performance of the Upper Limb (PUL) score, a measure of arm and hand function, declined an average of 1.8 points during the first treatment year, indicating loss of function as expected in a progressive disease like DMD. During the fourth year, the average decline was 0.6 points, suggesting that over longer treatment periods, deramiocel is slowing motor decline, according to Capricor.
New application will include findings from HOPE-3 study
In its next application, Capricor intends to supplement this data with findings from the HOPE-3 study. Topline results are “expected in the third quarter of 2025,” Marbán said.
This is a much larger trial than HOPE-2 that includes 104 participants at several locations across the U.S. These individuals, all male and at least 10 years old, will receive intravenous infusions of deramiocel or a placebo. The study will analyze safety and efficacy, with change in PUL score as the primary endpoint.
“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 DMD,” Marbán said. “While this was an unexpected decision by the FDA, we remain committed to the DMD community to get Deramiocel through the approval process.”
Previously, deramiocel for DMD received orphan drug status in both the U.S. and the European Union. This designation often grants additional regulatory assistance from the relevant agencies during the drug development process.
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