Phase 3 trial shows investigational cell therapy slowed disease progression in Duchenne muscular dystrophy

Researchers have reported positive results from the Phase 3 HOPE-3 clinical trial evaluating deramiocel, an investigational cell therapy infusion for Duchenne muscular dystrophy (DMD), a rare and progressive genetic disease that causes irreversible muscle weakness and heart damage.

The study, published in The Lancet, found that patients who received deramiocel experienced significantly slower disease progression compared with those receiving a placebo, demonstrating benefits across multiple measures of muscle and cardiac function.

Duchenne muscular dystrophy affects approximately 1 in 3,500 to 5,000 boys worldwide and progressively weakens skeletal, respiratory and cardiac muscles. While advances in care have improved survival, there remains a critical need for therapies to address multiple aspects of the disease, particularly in non-ambulatory patients with advanced disease.

In the HOPE-3 study, 106 participants with advanced DMD were randomized to receive quarterly infusions of deramiocel or placebo over 12 months. Patients treated with deramiocel showed significantly less decline in upper limb function, a critical measure of independence that affects activities such as feeding, grooming and using technology. The treatment also demonstrated advantages on measures of cardiac function and disease-related heart scarring, two major causes of illness and premature death in DMD.

"What makes these findings especially meaningful is that deramiocel demonstrated effects across multiple systems impacted by Duchenne muscular dystrophy," said Craig McDonald, chair of the Department of Physical Medicine and Rehabilitation at UC Davis Health and lead study investigator. "Preserving arm and hand function is critically important for maintaining independence and quality of life in people living with Duchenne. At the same time, protecting heart function is essential for long-term health. Seeing evidence of the benefit in both areas is a game changer and represents a potentially important advance for patients and families."

A different approach to treating Duchenne

Unlike therapies that target a specific genetic mutation, deramiocel is designed to address disease processes common to many people with DMD - including inflammation and fibrosis, or scarring - that progressively damages muscles and the heart.

The therapy consists of cardiosphere-derived cells, which are obtained from donated human heart tissue and act through biological signaling mechanisms that help reduce fibrosis and modulate harmful inflammation.

Researchers say this broad mechanism of action may allow the therapy to address both skeletal and cardiac muscle deterioration, making it distinct from mutation-specific treatments.

Key study findings

Among the study's Phase 3 findings, which confirmed the efficacy and safety of deramiocel in patients with advanced DMD:

• Patients receiving deramiocel experienced significantly less decline in upper limb function compared with placebo-treated patients.
• Imaging results showed evidence of reduced progression of heart muscle scarring, a hallmark of Duchenne-related cardiomyopathy.
• Multiple analyses of heart function favored deramiocel, with results consistently suggesting stabilization of cardiac performance.
• A composite analysis integrating functional outcomes, heart function and patient-reported assessments demonstrated a significant overall benefit for deramiocel.
• No deaths occurred during the study, and serious adverse events were uncommon.

Why the DMD study is unique

Researchers say HOPE-3 is notable because it evaluated outcomes that matter most to individuals living with advanced Duchenne, including the ability to perform everyday upper limb activities and measures of cardiac health. The trial also reflects years of clinical and preclinical research showing that deramiocel may help slow the progression of disease rather than treat a single symptom or genetic subtype.

Importantly, deramiocel is among the first investigational therapies in Duchenne to demonstrate evidence of disease modification across both skeletal and cardiac muscle systems in a Phase 3 study population largely composed of non-ambulatory patients, a group with significant unmet medical need.

About the HOPE-3 study

HOPE-3 was a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial. It evaluated quarterly intravenous infusions of deramiocel in patients with Duchenne muscular dystrophy. The study enrolled participants at leading neuromuscular centers across the United States, including UC Davis Health.