Dive Brief:
- Capricor Therapeutics hasn’t definitively proven that its experimental cell therapy benefits people with heart-related complications of Duchenne muscular dystrophy, a Food and Drug Administration panel concluded Wednesday.
- Capricor reported last year that its treatment, deramiocel, hit the main goals of a Phase 3 study in Duchenne patients with cardiomyopathy. But FDA scientists expressed skepticism about the data Capricor compiled and, by a 9-3 vote, the advisory panel determined the results didn’t show “substantial evidence” of the therapy’s effectiveness.
- The FDA rejected deramiocel last July but agreed to review a revised pitch from Capricor afterwards. The agency typically, though not always, sides with its advisory panels. It’s expected to make a decision on the company’s latest submission by Aug. 22.
Dive Insight:
Wednesday’s result is the latest twist in an unusual regulatory saga — and an important indicator of how flexible the FDA and its expert committees might be in assessing rare disease drugs going forward.
Public disputes between the FDA and makers of rare disease medicines were a sore spot under previous agency leadership, and reportedly among the reasons Marty Makary is no longer commissioner. Capricor was among those crying foul, as the company claimed to have aligned with agency officials on an approval package only to be blindsided when the FDA swatted away its application.
Since then, Capricor claimed a late-stage study showed deramiocel helped preserve upper limb function and the heart’s ability to pump blood in treatment recipients. Makary as well as former deputy Vinay Prasad left the agency. And the FDA has revived the approval chances of multiple drugs it had delayed or previously rejected, positioning the coming verdict on Capricor’s treatment as a potential barometer of FDA decisionmaking.
However, briefing documents submitted by FDA scientists ahead of the meeting revealed another disconnect between the Capricor and the agency. Reviewers argued deramiocel missed its initial Phase 3 study goals and that the benefits Capricor trumpeted were essentially a mirage aided by switching up a statistical analysis plan. Capricor countered that FDA staff relied on an older, irrelevant analysis, and the one it used was finalized before the study was unblinded.
What’s more, just as the meeting started, researchers published the full results of the Phase 3 trial in The Lancet. In it, investigators described deramiocel’s impact on Duchenne-related cardimyopathy, the leading cause of death among patients, as “not subtle.” But the paper also revealed the treatment had actually missed statistical significance on the purported heart benefits Capricor previously touted — leading Capricor to issue a clarification in a regulatory filing.
The dispute spilled over into the meeting. Capricor executives pointed to deramiocel’s effects on multiple measures of muscle function and defended the way the company analyzed those results. FDA reviewers argued the statistical changes Capricor employed “lack a scientific basis” and made the findings difficult to interpret.
Ultimately, most panelists referred to Capricor’s results as “fragile” and, as a result, not convincing enough despite the severity of the disease and urgent need for a new treatment.
“There is just not sufficient evidence for effectiveness, and it's unfortunate that for such a huge clinical need that we are unable to provide something,” said Mladen Vidovich, an interventional cardiologist at UI Health in Chicago.
“Believe me, I really, really want to see something work in this area. And there are some glimpses there. But I would not be able to at this time consider it strong support,” added John Teerlink, a professor of clinical medicine at the University of California, San Francisco.
The FDA did appear to leave an opportunity for a different outcome. Though panelists voted against the evidence in Duchenne-related cardiomyopathy specifically, they were encouraged to debate deramiocel’s impact on upper limb function. There, some advisers felt Capricor had a stronger case, albeit a still-unproven one.
The data on that measure were “a little more favorable,” said Christopher Coffey, a professor of biostatistics at the University of Iowa’s College of Public Health. “But I'm not convinced that [deramiocel] works.”
