공시 • Dec 16
Edgewise Therapeutics, Inc. Announces Positive Topline Results from the CANYON Phase 2 Trial of Sevasemten in Individuals with Becker Muscular Dystrophy
Edgewise Therapeutics, Inc. announced positive topline results from the Phase 2 CANYON trial of sevasemten in individuals with Becker muscular dystrophy. Sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor designed to protect muscle against contraction-induced damage in muscular dystrophies. The trial met its primary endpoint of change from baseline in CK. CANYON is the largest interventional trial to date in Becker and the first to achieve its primary endpoint. NSAA, the key secondary endpoint of function, showed a trend towards improvement over time in the sevasemten-treated group. Plasma fast skeletal muscle troponin I (TNNI2), a target-specific biomarker of fast skeletal muscle damage, showed a significant reduction, compared to placebo. Additional functional measures, including the 10-meter walk/run, 4-stair climb and 100-meter timed test, showed trends towards improvement compared to placebo. Notably, the treatment population had more advanced disease than placebo. Sevasemten was well-tolerated, and no new safety concerns were observed in either the adult or adolescent patient populations. Ninety-nine percent of eligible participants from CANYON and other sevasemten trials in Becker have enrolled in MESA, the ongoing open label extension trial. The Company is on track to complete recruitment in the GRAND CANYON cohort by the first quarter of 2025. Based on these positive Phase 2 results, the Company plans to engage the U.S. Food and Drug Administration (FDA) and European Medicines Agency about marketing authorization filing strategies for sevasemten in Becker. The Company intends to submit the complete results of the CANYON study for publication at a future medical congress. Overview of CANYON and Clinical Results: CANYON, the largest interventional Becker trial, is a Phase 2, double-blind, randomized, placebo-controlled study to investigate the effect of sevasemten on the safety, pharmacokinetics, biomarkers, and functional measures of participants (NCT05291091). The trial was not powered for the functional endpoints. Forty adults and 29 adolescents with Becker muscular dystrophy were enrolled. This study had a 4-week screening period, a 12-month treatment period, followed by a 4-week follow-up period. The adult participants were randomized to sevasemten or placebo in a 3:1 ratio. The adolescent participants were randomized in a 2:1 ratio to sevasemten or placebo and were assessed for safety and tolerability. The data analysis included the complete adult safety population of 40 individuals. There was a notable imbalance between adult participants in the sevasemten and placebo groups with the sevasemten group having more advanced disease at baseline based on all functional measures and MRI. Primary Endpoint: The primary endpoint to assess the efficacy of sevasemten compared to placebo was change from baseline in CK over the treatment period for adults. The results demonstrated a significant change from baseline in CK in the sevasemten-treated group (difference vs. placebo, 28% average decrease over months 6 through 12; p=0.02). Key Secondary Endpoint: The key secondary endpoint was the change from baseline in NSAA total score in adults at month 12. NSAA is a scale commonly used to rate motor function. The between-group difference was 1.1 points, favoring sevasemten; p=0.16 across all adult participants. NSAA remained stable over time in the sevasemten treatment group, similar to the observations in the ARCH study. Further, while the placebo group was small in number (n=12), NSAA declined similarly to that observed in previous natural history studies. Other Secondary Endpoints: Plasma TNNI2 decreased 77% from baseline in the sevasemten-treated group compared to placebo, averaged over months 6 through 12 in adults; p<0.001. The 10-meter walk/run, 4-stair climb and 100-meter timed test showed trends towards improvement, compared to placebo. The Company continues to evaluate additional secondary and exploratory endpoints. Safety and Tolerability: Sevasemten was well-tolerated, and no new safety concerns were identified. CANYON Implications to GRAND CANYON: The functional observations from the CANYON study support that the GRAND CANYON pivotal cohort’s primary endpoint is powered at >95% to demonstrate a statistically significant NSAA difference at 18 months. MESA, open label extension trial in adults with Becker: The Company is advancing MESA, an open-label extension trial to assess the long-term effect of sevasemten in individuals with Becker. MESA provides continued access to sevasemten to participants who were previously enrolled in ARCH, or completed CANYON, GRAND CANYON, or DUNE. To date, 99% of eligible participants completing these trials have enrolled in MESA. GRAND CANYON, a global pivotal cohort in Becker: GRAND CANYON, an expansion of the CANYON placebo-controlled trial, is a multi-center, randomized, double-blind, placebo-controlled cohort to evaluate the safety and efficacy of sevasemten in adults with Becker. The primary endpoint of GRAND CANYON is change from baseline in NSAA at 18 months. In addition, other functional assessments, biomarkers of muscle damage, MRI, patient-reported outcomes and safety will be assessed. GRAND CANYON is an 18-month cohort anticipated to recruit approximately 120 individuals with Becker. Data from GRAND CANYON, if positive, could support a marketing application. To learn more, go to clinicaltrials.gov (NCT05291091). Sevasemten has achieved notable regulatory milestones by securing FDA Orphan Drug Designation for the treatment of Becker and Duchenne, Rare Pediatric Disease Designation (RPDD) for the treatment of Duchenne, and Fast Track designations for the treatment of Becker and Duchenne. Further, sevasemten secured the EMA Orphan Drug Designations for the treatment of Becker and Duchenne.