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2.01eP Rationale, study design and baseline characteristics in the GRAND CANYON clinical trial of sevasemten in Becker muscular dystrophy adults
Abstract   Peer reviewed

2.01eP Rationale, study design and baseline characteristics in the GRAND CANYON clinical trial of sevasemten in Becker muscular dystrophy adults

Craig McDonald, Richard Roxburgh, Eugenio Mercuri, Kristl Claeys, Michela Guglieri, Erik H. Niks, Katherine Mathews, Anne M. Connolly, Luca Bello, Barry Byrne, …
Neuromuscular disorders : NMD, Vol.67(Suppl 1), 106709
09/29/2026
DOI: 10.1016/j.nmd.2026.106709

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Abstract

Becker muscular dystrophy (BMD) is a serious, rare, neuromuscular disorder with no approved therapies. Sevasemten is an investigational fast skeletal myosin inhibitor designed to protect muscle against contraction-induced damage and preserve function. Sevasemten is currently being investigated in Becker and Duchenne muscular dystrophy (BMD and DMD). Previous open label and placebo-controlled studies with sevasemten in adults and adolescents with BMD demonstrated reductions of muscle injury biomarkers and stabilization of NSAA. This diverges from published natural history in patients with NSAA ≤32, who were seen to have annual decreases in NSAA between 1 and 1.7 points. Targeting a similar population is anticipated to optimize the ability to detect meaningful clinical effects of a therapeutic intervention. GRAND CANYON (NCT05291091) is a global, multi-center, double-blind, placebo-controlled cohort to evaluate the efficacy and safety of sevasemten over 18 months in adults with BMD. Enrollment criteria included adults who are ambulatory, 18-50 years old with BMD with a North Star Ambulatory Assessment (NSAA) score 5-32, able to complete the 100-meter timed test in <200 seconds. Participants with a left ventricular ejection fraction <40%, predicted forced vital capacity <60%, and current or recent steroids treatment were excluded. Participants were randomized 2:1 to either 10 mg sevasemten or placebo, stratified by baseline NSAA and ability to rise from floor. The primary endpoint of GRAND CANYON is NSAA change from baseline at 18 months. Additional endpoints include timed function tests, stride velocity 95th percentile (SV95C), NSAD, lower extremity fat fraction on MRI, and biomarkers. Enrollment included 175 participants; the mean (SD) age was 33 (9) years. Only 4/175 (2%) of participants had mutations associated with minimal progression. Mean (SD) total NSAA score at Day 1 was 19.6 (7.6) with 58% of participants having a total NSAA score < 22. Mean (SD) 4-Stair Climb, 10-meter walk run, and 100-meter walk run tests were 6.3 (6.1), 8.2 (6.5), and 83.1 (33.8) seconds, respectively. Mean time for rise from floor was 5.4 (3.0) seconds for the 57% of participants were able to do so . Mean (SD) SV95C, as measured by the Syde activity monitor during the Screening period, was 1.2 (0.24) meters/second. Pre-treatment NSAA was strongly correlated with 4-Stair Climb velocity (r=0.90, p≤0.001), 10-meter walk run velocity (r=0.89, p≤0.001), 100-meter walk run velocity (r=0.82, p≤0.001), rise from floor velocity (r=0.87, p≤0.001), and SV95C (r=0.83, p≤0.001). Upper limb function was largely maintained, with 15% of participants having entry level Performance of Upper Limb (PUL 2.0) assessment <6. In the initial clinical global impression of disease severity (CGI-S), 51% of participants were assessed as having moderately or markedly severe disease symptoms. In the patient global impression of severity (PGI-S) 48% of participants indicated moderate or severe disease status. GRAND CANYON is the largest BMD interventional trial to date, with multiple endpoints that will provide insight into sevasemten effects on key functional manifestations of BMD. Positive results could support a regulatory marketing application to seek approval as the first targeted therapy for BMD.

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