Background
Becker (BMD) and Duchenne muscular dystrophy (DMD) are characterised by early and disproportionately affected fast (Type II) muscle fibers. EDG-5506 is an orally administered, once daily, investigational product that modulates fast skeletal muscle myosin. Decreased muscle damage biomarkers and fibrosis were seen in treated DMD disease models, while muscle strength and activity increased.
Objectives
ARCH is a 24-month Phase 1b open-label study to assess safety and PK with EDG-5506 in adults with BMD. Effects of treatment on biomarkers of muscle damage and function were also measured.
Results
12 adult ambulatory participants with BMD (mean NSAA 15.5) received daily oral doses of EDG-5506. After 12 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). Creatine kinase and myoglobin decreased from baseline to 12 months (p<0.01). Reduction in fast skeletal muscle troponin I (p<0.01) supported specific reduction in fast muscle fiber damage. NSAA changed by a mean +0.4 versus an expected decline of 1.2 predicted from natural history (Bello 2016, Van der Velde 2021).
Conclusions
Treatment with EDG-5506 was well tolerated and associated with rapid and sustained reductions in biomarkers of muscle damage. Trends toward improvements in function compared to expected natural history trajectories were observed with stable measures of strength. Phase 2 trials in BMD and DMD are ongoing (NCT05291091 and NCT05540860) with a pivotal cohort enrolling BMD adults. Additional data will be available at the time of presentation.