Fast (Type II) muscle fibers are affected early and disproportionately in dystrophinopathies. EDG-5506 is an investigational product that modulates fast skeletal muscle myosin and in animal models decreased muscle damage biomarkers and fibrosis, while increasing muscle strength and activity. A Phase 1 study including 7 adults with BMD showed favorable safety and pharmacokinetics (PK), with reduced muscle damage biomarkers after 14 days of EDG-5506._x000D_
ARCH is a 24-month Phase 1b open-label study designed to assess safety, tolerability, PK, changes in biomarkers, and function following long-term dosing with EDG-5506 in adults with BMD._x000D_
12 ambulatory participants with BMD aged 20-46y received daily oral doses of EDG-5506: 10 mg for 2 months, followed by 15 mg for 4 months, and then 20 mg. Baseline North Star Ambulatory Assessment (NSAA) ranged from 4-31 and North Star Assessment for Limb-Girdle Type Muscular Dystrophies (NSAD) from 7-50. EDG-5506 was well tolerated without serious adverse events, withdrawals, or dose modifications. Most common adverse events were dizziness and somnolence (n=3 participants each), typically briefly at initiation of dosing and self-resolving within a few days. Creatine kinase was reduced by a mean of 40% from baseline to 6 months and fast muscle troponin I (TNNI2) by 75% at last measurement (both p<0.01). At 6 months, NSAA increased from baseline by a mean +0.5 versus an expected decline of -0.6 (natural history data: Bello 2016, Van der Velde 2021), while NSAD increased by a mean +0.7. Other functional tests remained stable._x000D_ _x000D_ Conclusions_x000D_ EDG-5506 was well tolerated after 6 months of dosing. Biomarkers of muscle damage, including creatine kinase, and TNNI2, were consistently reduced. This was associated with trends toward improvements in function compared to the expected natural history trajectories. A Phase 2 trial is ongoing.