Edgewise Therapeutics (EWTX) Study Update summary

Study background and design

• Sevasemten (also known as Sevesantan) is a first-in-class fast myofibril myosin inhibitor developed for Becker muscular dystrophy, a rare, progressive neuromuscular disease with no approved therapies.

• The CANYON phase II trial was a multi-center, placebo-controlled study enrolling 69 ambulatory males aged 12–50, with adults forming the main efficacy cohort and adolescents included primarily for safety assessment.

• The primary endpoint was change in creatine kinase (CK) averaged across months 6, 9, and 12; key secondary endpoint was change in North Star Ambulatory Assessment (NSAA) at month 12.

• CANYON is the largest interventional study in Becker to date, conducted across 16 sites in three countries, with high patient retention and transition to open-label extension.

• The trial design was informed by prior studies and supports the ongoing pivotal GRAND CANYON trial, which is near full enrollment and powered to detect a clinically meaningful NSAA difference at 18 months.

Patient population and baseline characteristics

• Enrolled ambulatory males aged 12–50 years with dystrophin mutation and Becker phenotype, not on corticosteroids, and NSAA between 5–32.

• Adults were randomized 3:1 and adolescents 2:1 to sevasemten or placebo; the sevasemten group had more advanced disease at baseline.

• Functional measures at baseline were not well matched, with lower baseline NSAA scores in the sevasemten group.

• Slow progressor genotypes were largely excluded by functional cut-off criteria.

Key efficacy and safety results

• Sevasemten achieved the primary endpoint, showing a statistically significant 28% reduction in CK versus placebo (p=0.02), indicating reduced muscle damage.

• Plasma TNNI2, a fast skeletal muscle troponin biomarker, decreased by 77% from baseline versus placebo (p<0.001).

• 63% of sevasemten-treated patients showed stable or improved function at 12 months, compared to 33% on placebo (odds ratio 3.4).

• NSAA scores remained stable in the sevasemten group but declined in placebo, with a least-squares mean difference of 1.1–1.12 points favoring sevasemten at 12 months (p=0.16).

• Sevasemten was well tolerated, with no new safety signals; most common adverse events included headache, fatigue, dizziness, and somnolence, all transient and resolving spontaneously.