FDA advisors vote no to Capricor's DMD therapy
FDA advisors have voted that Capricor Therapeutics has not provided strong evidence of efficacy for its cell therapy for muscle problems associated with Duchenne muscular dystrophy, putting its approval in doubt.
There were already signs that Capricor could have a tough time at the advisory committee meeting when the FDA published a briefing document ahead of the meeting that poked holes in the efficacy data for deramiocel, which is based on donor cardiosphere-derived cells (CDCs) given by intravenous infusion.
As it turned out, the Cellular, Tissue, and Gene Therapies Advisory Committee (CTGTAC) was minded to agree with the FDA's assessment, voting by nine to three that the data submitted by Capricor for the cell therapy did not provide "substantial evidence" of efficacy.
Deramiocel was turned down by the FDA last year as a treatment for cardiomyopathy associated with DMD, but was subsequently refiled as a treatment for skeletal and cardiac manifestations of the muscle-wasting disease.
Shares in Capricor lost two-thirds of their value after the FDA published the briefing document, and remained weak after the advisory committee vote, which makes the chances of an approval now very shaky. The agency is due to deliver its verdict on the marketing application by 22nd August.
Panellists largely agreed with the FDA's assessment that changes to how the main supporting HOPE-3 clinical trial measured primary clinical outcomes – after it was completed – had made the analyses more complex and hard to interpret.
Capricor changed the measurement of heart-pumping capacity from direct changes in blood volume pumped per beat to a rank-based system of patient results, while upper limb function was calculated as a percentage change, rather than sticking to the original protocol of scores generated by a 42-point functional test.
The FDA reviewers' position was that, given these changes, HOPE-3 "did not meet its pre-specified primary and secondary efficacy endpoints, showing no statistically significant difference between deramiocel and placebo at 12 months." They also questioned whether the trial population had DMD cardiomyopathy, as their left ventricular ejection fraction (LVEF) scores were in the normal range on average at the start of the trial.
Capricor said it informed the FDA of the proposed changes last September, but received no feedback on the proposal before submitting its finalised application in November.
Just ahead of the advisory committee meeting, medical journal The Lancet published peer-reviewed results from HOPE-3, using Capricor's amended outcome measures, which the company said provides "external validation of the trial's design, statistical methodology, and findings."
The paper concludes there was a statistically significant 54% slowing of upper limb disease progression in the deramiocel group versus placebo, using the primary Performance of the Upper Limb (PUL) 2.0 scale, which Capricor said is a "substantial, meaningful effect in a population where functional decline is typically relentless and irreversible."
The company's chief executive, Linda Marbán, pointed out that this is the same data considered by the FDA and its expert advisors.
"We have continued to work with the FDA throughout its review, and we firmly believe this evidence supports approval," she said. "Deramiocel can change the course of this disease, and we are focused on our goal of bringing it to patients as the first approved cell therapy for Duchenne."
