Assess the effect of treatment with EDG-5506 on biomarkers of muscle damage and function in adults with Becker Muscular Dystrophy.

Fast (Type II) muscle fibers are affected early and disproportionately in Becker (BMD) and Duchenne muscular dystrophy (DMD).  EDG-5506 is an orally administered, once daily, investigational product that modulates fast skeletal muscle myosin and, in DMD disease models, decreased muscle damage biomarkers and fibrosis while increasing muscle strength and activity.

12 adult ambulatory participants with BMD received daily oral doses of EDG-5506. At baseline, North Star Ambulatory Assessment (NSAA) ranged from 5 to 31, with decreased muscle mass as evidenced by low serum creatinine and DXA, and functional loss with mean NSAA 15.5.  After 18 months, EDG-5506 was well tolerated without serious adverse events, withdrawals due to AE, or dose modifications. Most common adverse events were dizziness (n=4), somnolence (n=3) and COVID-19 (n=3).  Dizziness/somnolence were typically at dose initiation and self-resolved within a few days. Creatine kinase decreased by a mean 41% from baseline to 18 months and myoglobin by 35%.  Reduction in fast troponin I showed specific reduction in fast muscle fiber damage.  NSAA changed by a mean +0.2 versus an expected decline of -1.8 predicted from natural history (Bello 2016, Van der Velde 2021).

EDG-5506 was well tolerated with rapid and sustained reductions in biomarkers of muscle damage.  Trends toward improvements in function compared to expected natural history trajectories were observed.  Phase 2 trials in BMD and DMD are ongoing (NCT05291091 and NCT05540860) with a cohort designed to be registrational enrolling in BMD.