Introduction/aims: Sevasemten (EDG-5506) is an orally administered, investigational small molecule that selectively modulates fast muscle fiber contraction by inhibiting fast myosin ATPase. This study assessed the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of sevasemten in healthy adult volunteers (HVs) and adults with Becker muscular dystrophy (BMD).
Methods: This randomized, double-blind, placebo-controlled phase 1 study was conducted at a single site. Eligible participants were 18-55 years of age with a body mass index < 30 kg/m2; adults with BMD were required to have a confirmed diagnosis based on documentation of pathogenic variant(s) in the dystrophin gene and a BMD phenotype. Participants were randomized 3:1 to receive sevasemten or placebo for up to 14 days. Endpoints included adverse events (AEs), sevasemten PK and muscle concentration, and changes in biomarkers of muscle injury.
Results: The study enrolled 97 HVs in 7 single-dose cohorts (N = 57) and 5 multiple-dose cohorts (N = 40). Seven adults with BMD were enrolled in a multiple-dose cohort. There were no serious AEs or AEs leading to trial discontinuation; the most common AEs were dizziness and somnolence. For adults with BMD, serum biomarkers of muscle injury trended down progressively with sevasemten treatment (average maximal reductions of 70% for creatine kinase, 98% for fast skeletal muscle troponin I, and 45% for myoglobin). Plasma proteomic analysis identified a signature of 125 elevated proteins characteristic of BMD that was reversibly lowered with sevasemten treatment.
Discussion: Sevasemten was generally well tolerated. Preliminary observations of decreases in biomarkers of muscle damage in adults with BMD support further clinical development.
Trial registration: NCT04585464.
Keywords: Becker muscle dystrophy; EDG‐5506; contraction‐induced damage; sevasemten.
© 2025 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.