A Phase 1, Double-Blind, Placebo-Controlled Trial of Sevasemten (EDG-5506), a Selective Modulator of Fast Skeletal Muscle Contraction, in Healthy Volunteers and Adults With Becker Muscular Dystrophy.

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.