MDA 2024: Limb, heart function preserved with DMD cell therapy

Positive results of Phase 3 trial expected to support FDA application

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

An illustration of a heart muscle helps to illustrate a graphic for the 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference.

The investigational cell therapy CAP-1002 has continued to slow declines in upper limb and heart function among boys and young men with Duchenne muscular dystrophy (DMD), according to two-year results from the HOPE-2 open label extension (OLE) study.

The findings were presented at the recent 2024 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference by Mark Awadalla, vice president of clinical operations at Capricor Therapeutics, which is developing CAP-1002.

“We really believe that CAP-1002 has the potential to be a backbone therapy, whether the patient is on exon-skipping, or [has] been exposed to gene therapy, or [is] just on steroids,” Awadalla said. “We believe that CAP-1002 can be administered in conjunction with any therapy.”

The talk was titled “CAP-1002: An Allogeneic Cell Therapy Demonstrates Disease Modification in Later Stage DMD Patients – 24-Month Safety and Efficacy Results from the HOPE-2 Open Label Extension.

A pivotal placebo-controlled Phase 3 trial called HOPE-3 (NCT05126758) is underway, and males, ages 10 and older, with DMD are being recruited at several U.S. sites.

A data readout is expected this year and positive results will support a regulatory application to the U.S. Food and Drug Administration (FDA). Meanwhile, HOPE-2-OLE participants are continuing treatment and more updates are expected this year.

“We plan to discuss options for potential expedited approval pathways with the FDA and, in connection with these efforts, look forward to sharing the three-year results in the second quarter of this year,” Linda Marbán, PhD, CEO of Capricor, said in a company press release.

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The goal of CAP-1002 is late-stage DMD patients

DMD patients lack dystrophin, a protein important for muscle health. Progressive muscle weakness and wasting affects the limbs and the muscle of the heart.

Awadalla said disease of the heart muscle, or cardiomyopathy, is “almost universal” in DMD, with nearly all patients having manifestations of it by early adulthood. It’s also the leading cause of death in DMD, but there are no approved therapies for heart disease in these patients, according to the researcher.

CAP-1002 consists of cardiosphere-derived cells from healthy donated heart muscle. When the cells are infused into the bloodstream, they circulate and release small vesicles taken up by target cells, including heart muscle cells, where they release their cargo to have immunomodulatory, anti-inflammatory, and regenerative effects.

Awadalla said CAP-1002 has been infused in more than 200 people across several indications to date, but noted the company’s primary target population is late-stage DMD patients, who should see slower declines in skeletal and cardiac muscle function with treatment.

The Phase 2 HOPE-2 clinical trial (NCT03406780) enrolled 20 boys and young men with relatively advanced DMD. They were randomly assigned to receive CAP-1002 infusions (150 million cells) into the vein, or intravenously, or a placebo once every three months for a year while still on standard-of-care corticosteroids.

CAP-1002 led to a significant, 71% slowing of upper limb function declines relative to the placebo after a year, as assessed by the Performance of the Upper Limb (PUL 1.2), results showed.

Heart function was also preserved relative to the placebo and was shown by stabilizations in left ventricular ejection fraction (LVEF), an indicator of how well the heart pumps blood to the rest of the body during a heartbeat, on cardiac MRI imaging.

Following a gap of a little over a year, during which patients continued to be monitored without treatment, 13 HOPE-2 participants entered the OLE, where all are receiving CAP-1002. The patients were mean age of 13 and none were able to walk.

Consistent with previous interim analyses, trial participants continue to see slowed declines in upper limb function after two years.

The mean decline in PUL 2.0 scores was about 2.8 points across the two-year OLE, regardless of whether patients had initially been assigned to the placebo or active treatment in the main trial.

That’s slower — by 4.9 points — than the 7.7-point decline seen by the original placebo group when they were left untreated for two years between the main trial and the gap period.

CAP-1002 was associated with a 64% slowing of disease progression overall.

“To us, this data is indicative of a disease-modifying potential and supports treatment earlier in the patient’s life,” Awadalla said. “We’re very excited about this.”

Among nine patients with available cardiac MRI scans, six have seen LVEF improvements since the end of the main HOPE-2 trial.

The average yearly 2.5% increase in LVEF for these patients is a notable contrast from the natural history of the disease, where patients see yearly declines of around 0.75%, according to Awadalla.

“Time is muscle for these patients,” Awadalla said, noting that once muscle function is lost, it can’t be regained. “CAP-1002 demonstrates the potential to slow disease progression.”

The treatment also has continued to be associated with a favorable safety profile across analyses.