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

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked genetic disease of skeletal and cardiac muscle that leads to loss of ambulation and premature death due to progressive myopathy and cardiomyopathy. Deramiocel, a heart-derived cellular therapy consisting of human allogeneic cardiosphere-derived cells, improved cardiac and skeletal muscle function in phase 1-2 studies of DMD. Our aim was to assess the efficacy and safety of deramiocel in advanced DMD and support the findings of HOPE-2.

METHODS: HOPE-3, a phase 3, multicentre, randomised (1:1), double-blind, placebo-controlled study, included participants aged 10 years or older with DMD. Investigational product was infused intravenously every 3 months in outpatient settings. Skeletal and cardiac function was evaluated at 12 months. The primary endpoint was total Performance of the Upper Limb 2.0 (PUL2.0) percentage change from baseline. The trial is registered with ClinicalTrials.gov (NCT05126758).

FINDINGS: Between June 22, 2022, and May 28, 2024, 139 participants were screened, of whom 106 were randomly assigned to deramiocel (n=54) or placebo (n=52), and included in the intention-to-treat population. The primary endpoint showed significant improvements in the deramiocel group versus placebo. For total PUL2.0, least-squares mean percentage change at 12 months favoured deramiocel by 4·55% (95% CI 0·47-8·63; p=0·029). The safety profile of deramiocel was similar to that of placebo.

INTERPRETATION: Deramiocel safely slows disease progression in advanced DMD, preserving skeletal muscle function. Administered quarterly in a simple outpatient regimen, deramiocel is a promising treatment for DMD, agnostic to the precise underlying genetic lesion.

FUNDING: Capricor Therapeutics.