Sevasemten is an investigational selective inhibitor of fast skeletal muscle myosin in development for treatment of Becker muscular dystrophy (BMD) by protecting against contraction-induced muscle injury. Results from an open-label study (ARCH) with seva demonstrated sustained lowering of circulating biomarkers associated with muscle injury, such as creatine kinase (CK), fast skeletal troponin I (TNNI2), and myoglobin (Mb), over a 2-year period. The CANYON Phase 2 clinical trial (NCT05291091) was a randomized, double-blind, placebo-controlled study evaluating the efficacy of Sevasemten versus placebo in subjects with BMD over a period of 1 year. Here, we present injury-associated proteomic changes in response to Sevasemten treatment that differentiate from the placebo treatment group.
In adults treated with 10 mg Sevasemten daily, significant reductions relative to placebo (p < 0.0001) were observed within 1 month of treatment in a broad panel of proteins previously identified as associated with muscle injury, with sustained reduction through 6 – 12 months (p < 0.0001). The most responsive proteins were TNNI2 (p < 0.001), fast skeletal regulatory light chain (p < 0.001), and Calpain-3 (p < 0.001). The one-year changes observed in muscle injury proteins in the placebo subgroup did not differentiate from natural history (p = 0.1), while the Sevasemten subgroup was significantly reduced relative to natural history (p < 0.001). While a wide range of individual responses to Seva treatment was observed, individuals with higher levels of muscle injury proteins at baseline tended to be more responsive to Sevasemten than those with lower injury levels.
This study is the largest completed placebo-controlled interventional trial in BMD; these findings demonstrate that Sevasemten reduces muscle injury biomarkers in adults with BMD, supporting the potential to preserve muscle and function.