Experimental treatment may preserve upper limb function in DMD
Long-term trial data show promise for deramiocel, Capricor says
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Boys and young men with Duchenne muscular dystrophy (DMD) who switched from a placebo to the experimental cell therapy deramiocel as part of a clinical trial showed smaller declines in measures of upper limb function after making the change, new data show.
Data from the study, which included nearly 100 patients followed for two years, also suggested that the rate of upper limb function decline was consistent — and lower than would be expected without treatment — among patients who received deramiocel throughout the trial.
Capricor Therapeutics, the company developing deramiocel, shared the data earlier this month at the 31st Annual Congress of the World Muscle Society in Hiroshima, Japan.
The new analyses were also included in Capricor’s recent amendment to its application seeking approval of deramiocel in the U.S. A decision from the U.S. Food and Drug Administration (FDA) is expected by Nov. 22.
“These results add to a growing body of evidence for Deramiocel,” Linda Marbán, PhD, Capricor’s CEO, said in a company press release.
Upper limb function key to independence
DMD is a genetic disease mainly affecting boys and men. It is marked by progressive muscle weakness, and most patients are unable to walk by the time they reach adolescence. That makes arm and hand function especially important.
“Upper limb function is critical to quality of life for young men with DMD because it is directly tied to their independence,” said Craig McDonald, MD, chair of the physical medicine and rehabilitation department at the University of California Davis Health. “Their arms are how they feed themselves, control their wheelchairs and use their phones, and how they stay independent.”
Deramiocel uses cardiosphere-derived cells, which are immature heart cells thought to help reduce inflammation and promote muscle regeneration. The treatment is given by infusion into the bloodstream.
Capricor’s application seeking FDA approval of deramiocel is based largely on data from the Phase 3 HOPE-3 clinical trial (NCT05126758), which tested the therapy against a placebo in DMD patients ages 10 and older. The study’s main goal was to see if deramiocel was better than the placebo at improving a measure of upper limb function called the Performance of the Upper Limb test, version 2 (PUL 2.0).
According to Capricor, the study met its goal, with one-year results showing statistically significant benefits for PUL 2.0 with deramiocel relative to a placebo. The company has said the study also met a key secondary goal, as deramiocel outperformed the placebo on a measure of heart function.
But the FDA has called these results into question, saying that Capricor altered its statistical plan and that, under the original analysis plan, deramiocel didn’t show significant benefit relative to the placebo on PUL 2.0 or heart health measures. An FDA advisory committee recently found that available evidence does not support deramiocel as an effective treatment for heart disease in DMD.
The new analysis covers data from nearly 100 patients who participated in HOPE-3. After the yearlong placebo-controlled part of the trial ended, these participants entered into an open-label study in which all are being treated with deramiocel and followed for long-term outcomes.
Marbán said the open-label data so far “aligns with our previous clinical studies, which together show the same pattern across multiple years of treatment.”
“The FDA has received these data as part of the recent major amendment to the Deramiocel Biologics License Application, along with extensive sensitivity and robustness analyses we produced to support the results of the HOPE-3 randomized clinical trial,” Marbán said. “We will continue to work with the FDA through the remainder of the review.”
Scores show slower decline after switch to deramiocel
The new analyses cover findings up to two years. Among patients who were on deramiocel the whole time, mean rates of decline on the PUL 2.0 were relatively consistent: 0.95 in the first year and 0.89 in the second.
For patients who were initially on the placebo, PUL 2.0 scores worsened by a mean of more than 2 points during that year. But in the second year, after patients switched to deramiocel, scores showed a slower decline of 0.49 points.
“When the young men who had been declining on placebo started Deramiocel, their rate of upper limb loss dropped by roughly 75% in their first year of treatment,” said McDonald, principal investigator on the trial. “Just as important, patients who were on Deramiocel both years declined at a similar rate in year 1 and year 2, which suggests that the slower decline was triggered by starting treatment, not the passage of time.”
In a subset of patients who were evaluated at two years, mean PUL 2.0 scores declined by less than four points: 3.42 for patients who were on deramiocel the whole time, and 3.76 for those who were on the placebo the first year. By comparison, in natural history groups, similar patients experienced PUL 2.0 declines of more than five points over the same time period.
“Being able to follow the same young man before and after he starts treatment is a powerful way to see a treatment effect, and what we saw was consistent with the randomized, placebo-controlled period,” McDonald said. “As a clinician seeing these patients, I have had very little to offer them that could meaningfully slow the progression of upper limb functional loss once they were non-ambulant. These data suggest there could be a way to treat this aspect of the disease.”
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