Abstract Details

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.

ARCH is a 24-month Phase 1b open-label study designed to assess safety and PK with EDG-5506 in adults with BMD. Effects of treatment on biomarkers and function were also measured.

12 ambulatory participants with BMD aged 20-46y received daily oral doses of 10-15 mg EDG-5506 for 6 months. 

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 at initiation of dosing and self-resolving within a few days. Creatine kinase (CK) decreased by a mean of 40% from baseline to 6 months and fast skeletal muscle troponin I (TNNI2) decreased by 75% at last measurement (both p<0.01), while NSAA increased from baseline (4-31) by a mean +0.5 versus an expected decline of -0.6 (natural history data: Bello 2016, Van der Velde 2021). Plasma proteomics, measured with the 7K Somascan® Assay platform confirmed decreases in CK and TNNI2; further over 6 months there was evidence of progressive change in inflammatory proteins toward a profile of unaffected individuals.

EDG-5506 was well tolerated up to 6 months of dosing with consistent reductions in biomarkers of muscle damage demonstrating target engagement.  Proteomic profiles following treatment showed not only rapid and sustained improvements in proteins characteristic of muscle damage but also longer term changes in inflammatory proteins towards levels measured in unaffected individuals. This was associated with trends toward improvements in function compared to the expected natural history trajectories. Phase 2 trials in BMD and DMD are ongoing.