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Deramiocel Shows Promise in Addressing Heart Failure in Duchenne Muscular Dystrophy
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Key Takeaways
- Deramiocel targets cardiomyopathy in Duchenne muscular dystrophy, a genetic disorder causing muscle weakness and heart failure due to dystrophin deficiency.
- Composed of cardiosphere-derived cells, deramiocel has shown immunomodulatory and regenerative effects in heart failure, shifting macrophages to a healing phenotype.
Duchenne muscular dystrophy is an incurable neuromuscular disorder that can lead to cardiomyopathy, resulting in heart failure.
Capricor Therapeutics completed submission of their biologics license application to the FDA, seeking approval for deramiocel (CAP-1002) for patients with Duchenne muscular dystrophy (DMD) cardiomyopathy. If accepted, it would be the first approved therapy for this disease.
Man with muscular dystrophy in wheelchair flexing arm muscle | Image Credit: © Montri - stock.adobe.com
DMD is an incurable genetic disorder characterized by progressive weakness and chronic inflammation of the skeletal, heart, and respiratory muscles. This is caused by a lack of functional dystrophin, a protein that provides structural support to muscle cells. Without enough dystrophin, muscle cells suffer extensive damage, leading to their death and replacement by fibrotic tissue. The heart is also impacted by this process, as dying cardiac muscle cells are replaced by scar tissue. Over time, this results in cardiomyopathy and eventually heart failure (HF), which is the leading cause of death in patients with DMD.1
According to the CDC, approximately 1 in every 5000 males between the ages of 5 and 9 years old, affecting an estimated 15,000 to 20,000 individuals in the United States. Patients with DMD have a median age of survival of 23.7 years and limited treatment options. Standard of care typically includes steroids, cough assist, and scoliosis surgery.2
Deramiocel is comprised of cardiosphere-derived cells (CDCs), a type of stromal cell shown in both preclinical and clinical studies to have strong immunomodulatory, antifibrotic, and regenerative effects in HF. These cells work by releasing exosomes, which influence the shift from a pro-inflammatory state to a healing phenotype in macrophages.1
The submission is supported by data from the phase 2, randomized, double-blind, placebo-controlled trial HOPE-2 trial (NCT03406780) evaluating safety and efficacy of intravenous delivery of allogeneic CDCs in subjects with DMD, ages 10 years or older with moderate upper limb impairment. Investigators enrolled a total of 26 patients who were randomly assigned in a 1:1 ratio to receive either deramiocel (1·5 × 108 CDCs; n=8) or placebo (n=12) intravenously every 3 months for a total of 4 infusions. The primary outcome measured was change in mid-level elbow Performance of Upper Limb version 1.2 (PUL 1.2) score at 12 months, assessed in the intention-to-treat population, as well as safety.3,4
In patients who underwent a post-treatment PUL 1.2 assessment (8 in the deramiocel group and 11 in the placebo group), deramiocel showed a greater mean improvement in mid-level elbow PUL 1.2 scores over 12 months compared with placebo (percentile difference: 36.2, 95% CI: 12.7–59.7; mean difference: 2.6 points; p=0.014).4
The safety profile was favorable, and infusion-related hypersensitivity reactions occurred in 3 patients, of which 1 discontinued treatment due to a severe allergic reaction. No other major adverse events were reported, and no deaths occurred.4
“This BLA is the culmination of a body of work that has been focused on bringing this potentially transformational therapy to those patients in need,” said Linda Marbán, PhD, chief executive officer of Capricor, in a press release. “We believe that the strength of this application is that deramiocel has shown in multiple clinical trials attenuation of the cardiac implications of DMD.”1
