Cell Therapy Slows Upper Limb Decline in Duchenne Muscular Dystrophy

The investigational cell therapy deramiocel slowed upper limb functional decline in boys and young men with Duchenne muscular dystrophy, data from the phase III HOPE-3 trial showed.

At 12 months, the mean percent change from baseline in Performance of Upper Limb 2.0 (PUL 2.0) total score was −3.86 in the deramiocel group and −8.41 in the placebo group, a difference of 4.55 (P=0.029), reported Aravindhan Veerapandiyan, MD, of Arkansas Children’s Hospital and the University of Arkansas for Medical Sciences in Little Rock.

This represented a 1.2-point difference on the PUL 2.0, corresponding to a 54% slowing of disease progression in 1 year, Veerapandiyan said in a late-breaking science session at the American Academy of Neurology annual meeting.

Secondary endpoints included PUL 2.0 mid-level domain scores, which are closely linked to independence, and the Duchenne Video Assessment “Eat 10 Bites” score, which measures sustained feeding performance in a home setting. Mid-level PUL 2.0 scores indicated a 65% slowing of progression (P=0.008). The Eat 10 Bites scores at 12 months showed that deramiocel reduced decline in independent feeding by 83%.

Deramiocel also preserved left ventricular fraction (LVEF) and slowed late gadolinium enhancement (LGE), a measure of cardiac fibrosis, Veerapandiyan said. In LVEF, the treatment difference was 2.4% (P=0.041) at 12 months; in LGE, it was -3.0 segments (P=0.022). The therapy was safe and well tolerated, he added.

“The study met all the primary and secondary endpoints, showing both benefit in the skeletal muscle as well as cardiac,” Veerapandiyan stated.

Duchenne muscular dystrophy is caused by mutations in the DMD gene. Loss of the protein dystrophin triggers a cascade of effects, including progressive degeneration of skeletal and cardiac muscle, a pro-inflammatory and pro-fibrotic immune response that impairs repair, and a steady decline in function that can culminate in life-threatening cardiac events. The condition primarily affects males.

Deramiocel is a novel cellular therapy that demonstrated benefit on skeletal muscle function in the HOPE-2 phase II study of Duchenne and its open-label extension. The treatment consists of allogeneic cardiosphere-derived cells that have been shown to confer immunomodulatory and anti-fibrotic properties.

The phase III HOPE-3 trial assessed the efficacy and safety of deramiocel in late-ambulatory and non-ambulatory male Duchenne patients. The double-blind study randomized 106 Duchenne patients at least 10 years old to quarterly infusions of deramiocel (54 participants) or placebo (52 participants).

At enrollment, patients had a PUL 2.0 entry item score of at least 2 and an LVEF of at least 35%. All patients were on background stable corticosteroid therapy.

PUL 2.0 is a functional scale of upper limb performance, Veerapandiyan noted. The entry item begins with a starter task that establishes a patient’s starting point on a 0 to 6 scale. The full assessment reflects the proximal-to-distal progression seen in Duchenne and includes 22 items across three domains: shoulder, elbow, and distal function. The maximum possible score is 42.

In HOPE-3, participants had a mean age of 15 years. Most (84.9%) were non-ambulatory, and 24.5% were receiving exon-skipping therapy. Just under half (45.3%) had a PUL 2.0 entry item score of 2 or 3, while the remainder scored 4, 5, or 6.

The overall safety profile of deramiocel was comparable to placebo, Veerapandiyan said. “The mild-to-moderate adverse events that were related to deramiocel were more frequent in the treated group, and this consisted of flu-like symptoms that were transient and resolved within 24 to 48 hours after infusion,” he pointed out. One serious adverse event occurred in the deramiocel group (1.9%) and five occurred in the placebo group (9.6%).

In July 2025, the FDA rejected a biologics license application from Capricor Therapeutics, citing insufficient clinical evidence from the HOPE-2 trial and requesting additional data. The agency is now re-evaluating the application with results from HOPE-3 and is expected to issue a decision by August 22.