Deramiocel heart-derived cellular therapy in advanced Duchenne muscular dystrophy (HOPE-3): a phase 3, randomised, double-blind, placebo-controlled trial.

Summary

HOPE-3 randomized 106 participants with advanced Duchenne muscular dystrophy to quarterly intravenous deramiocel or placebo. At 12 months, the total Performance of the Upper Limb 2.0 score favored deramiocel by 4.55 percentage points, with a 95% confidence interval of 0.47-8.63 and P=0.029. The treatment was similarly safe to placebo and represents phase 3 evidence for a heart-derived allogeneic cardiosphere-derived cell therapy affecting both skeletal and cardiac disease.

Key Findings

• 106 participants were randomized to deramiocel or placebo in the intention-to-treat population.
• At 12 months, total PUL2.0 percentage change favored deramiocel by 4.55 percentage points, with a 95% CI of 0.47-8.63 and P=0.029.
• The safety profile of deramiocel was similar to that of placebo.

Clinical Implications

Quarterly outpatient deramiocel may become a treatment option for patients aged 10 years or older with advanced Duchenne muscular dystrophy if findings are confirmed by regulatory review and longer-term follow-up. Cardiac surveillance remains important because the disease includes progressive cardiomyopathy, even when the principal measured benefit is skeletal muscle function.

Limitations

• The sample size was modest at 106 participants, limiting precision for uncommon adverse events and subgroup analyses.
• The primary efficacy assessment was limited to 12 months, so durability of benefit and long-term cardiac outcomes require further evaluation.

Future Directions

Longer follow-up should determine whether deramiocel alters the trajectory of cardiomyopathy, preserves ambulatory and upper-limb function over several years, and improves survival. Studies should also evaluate optimal treatment timing, biomarkers of response, and comparative effectiveness against contemporary Duchenne muscular dystrophy standards of care.