Edgewise Therapeutics announced positive topline results from its Phase 2 CANYON trial evaluating sevasemten in individuals with Becker muscular dystrophy (BMD). The trial achieved its primary endpoint, demonstrating a statistically significant reduction in creatine kinase (CK) levels, a key biomarker of muscle damage.
The CANYON trial, the largest interventional study in Becker muscular dystrophy to date, enrolled 40 adults and 29 adolescents with BMD. Adult participants were randomized to receive either sevasemten or placebo for a 12-month treatment period. The primary endpoint was the change from baseline in CK levels.
Primary Endpoint Achieved
Results from the CANYON trial showed a 28% average decrease in CK levels in the sevasemten-treated group compared to placebo over months 6 through 12 (p=0.02). This significant reduction in CK indicates that sevasemten effectively reduces muscle damage associated with BMD.
Secondary Endpoint Shows Functional Stabilization
In addition to the primary endpoint, the trial assessed the North Star Ambulatory Assessment (NSAA), a key secondary endpoint measuring motor function. While the between-group difference of 1.1 points favoring sevasemten was not statistically significant (p=0.16), the NSAA scores remained stable over time in the sevasemten group, contrasting with the decline typically observed in natural history studies of BMD.
Craig M. McDonald, M.D., a Principal Investigator in the CANYON trial, noted, "This landmark study presents compelling biomarker data and promising signals that suggest the potential for functional stabilization with administration of sevasemten."
Additional Biomarker Data
Further analysis revealed a 77% decrease from baseline in plasma fast skeletal muscle troponin I (TNNI2), another biomarker of muscle damage, in the sevasemten-treated group compared to placebo (p<0.001). Trends towards improvement were also observed in other functional measures, including the 10-meter walk/run, 4-stair climb, and 100-meter timed test.
Safety and Tolerability
Sevasemten was well-tolerated in both adult and adolescent participants, with no new safety concerns identified during the trial.
Implications for Future Development
Based on these positive Phase 2 results, Edgewise Therapeutics plans to engage with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to discuss marketing authorization strategies for sevasemten in Becker muscular dystrophy. The company is also on track to complete recruitment for the GRAND CANYON cohort, a pivotal study evaluating sevasemten in a larger population of individuals with BMD, by the first quarter of 2025.
Joanne Donovan, Ph.D., M.D., Chief Medical Officer at Edgewise, stated, "We are very encouraged by the CANYON results in Becker and the potential of this novel muscle-targeted therapeutic."
About Sevasemten
Sevasemten is an orally administered, first-in-class fast skeletal myosin inhibitor designed to protect muscle against contraction-induced damage in muscular dystrophies. It is also being studied in Phase 2 trials for Duchenne muscular dystrophy.
