FDA advisers reject evidence for Duchenne heart therapy
Panel’s 9-3 vote was nonbinding; final FDA decision is due Aug. 22
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An advisory committee to the U.S. Food and Drug Administration (FDA) has voted that available evidence does not support the effectiveness of the experimental cell therapy deramiocel for treating heart muscle disease in people with Duchenne muscular dystrophy (DMD).
In a company press release, Capricor Therapeutics, the therapy’s developer, said the question before the committee addressed a narrower indication than the company had applied for. Capricor also stressed that the committee did not vote on deramiocel’s overall benefit-risk profile. According to the company, the committee’s feedback in a separate discussion was directionally supportive of the therapy’s effects on upper-limb function.
Capricor still seeking FDA approval after advisory vote
“We remain committed to deramiocel and to the patients who could benefit from it,” said Linda Marbán, PhD, Capricor’s CEO. The company is “focused on working with the FDA toward potential approval.”
The FDA is currently reviewing an application seeking approval of deramiocel as a treatment for heart muscle disease, or cardiomyopathy, in people with DMD. A final decision is expected by Aug. 22.
When reviewing such applications, the agency sometimes asks for input from advisory committees, which are groups of independent experts. Along with presentations of company data, these meetings allow people with the disease, caregivers, clinicians and advocates to share their perspectives and experiences.
In this case, the FDA asked for feedback from its Cellular, Tissue, and Gene Therapies Advisory Committee, which met last week. After reviewing the available data, the committee was asked to vote on whether the evidence supported deramiocel’s effectiveness in treating DMD-related cardiomyopathy. Three of the committee’s 12 members voted yes, while nine voted no.
The committee’s vote is advisory and nonbinding, meaning the FDA will consider its recommendation but is not required to follow it.
The Muscular Dystrophy Association (MDA), along with other advocacy organizations, will hold a meeting today at 1 p.m. ET to discuss the advisory committee vote and what comes next.
“We know [the committee’s] vote is deeply disappointing for many in the Duchenne community – the room was heavy with the frustration the Duchenne community feels,” Paul Melmeyer, MDA’s executive vice president of public policy and advocacy, said in an association press release.
“But we are immensely grateful to every community member who submitted comments, and particularly those who traveled to Maryland to testify,” Melmeyer added. “They did an excellent job emphasizing that muscle loss and heart function continue to decline over time, and families cannot get that time back.”
Deramiocel tested for muscle and heart function in DMD
DMD is a genetic disorder marked by progressive muscle damage and weakness. The disease affects skeletal muscles, which control movement, as well as the heart muscle. There are currently no FDA-approved treatments for DMD-related cardiomyopathy, which is a leading cause of death in people with the disease.
Deramiocel is designed to preserve skeletal and heart muscle function in DMD. It contains cardiosphere-derived cells, which are derived from heart tissue and release signaling molecules thought to reduce inflammation and scarring.
Capricor originally applied for the therapy’s approval based on results from a Phase 2 clinical trial called HOPE-2 (NCT03406780) and its open-label extension, but the FDA declined to approve the application, saying more clinical data were needed to demonstrate the therapy’s efficacy.
The company then ran the larger Phase 3 HOPE-3 trial (NCT05126758), which tested deramiocel against a placebo in 106 people with DMD. Most participants could not walk, and more than three-quarters had a clinical diagnosis of cardiomyopathy.
The study’s main goal was to see if deramiocel led to better outcomes on the Performance of the Upper Limb test, version 2 (PUL 2.0), a standardized measure of arm and hand function. A key secondary goal was to see if the therapy would improve left ventricular ejection fraction (LVEF), a measure of how well the heart pumps blood to the body.
Late last year, Capricor announced that HOPE-3 had met both goals: participants given deramiocel showed statistically significant improvements in PUL 2.0 and LVEF compared with those on the placebo.
Full results from the trial, recently published in The Lancet after peer review, showed a statistically significant benefit with deramiocel on the primary PUL 2.0 endpoint. The key secondary LVEF endpoint favored deramiocel but did not reach statistical significance.
FDA disputes Capricor’s reading of HOPE-3 results
However, the FDA has taken issue with Capricor’s interpretation of the results. The agency said Capricor did not follow the prespecified statistical plan for assessing the trial results. According to the FDA, under the original statistical analysis plan, neither PUL 2.0 nor LVEF showed a statistically significant difference between deramiocel and placebo.
In briefing documents released prior to the advisory committee meeting, the FDA said that HOPE-3 “demonstrates small and variable changes in measures of upper limb skeletal muscle function and in several [heart] imaging parameters that did not reach statistical significance and are, thus, difficult to interpret.”
Given that deramiocel has observed safety risks, such as hypersensitivity reactions, including anaphylaxis, “the benefit-risk assessment for deramiocel appears unfavorable in the absence of evidence of effectiveness,” the FDA said.
Capricor disputed the FDA’s conclusions before the committee meeting, saying the agency relied on an old, incomplete draft of HOPE-3’s analysis plan rather than the final plan completed before unblinding. The company said the final plan included content specifically requested by the FDA.
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