CANYON trial results: Sevasemten, an investigational fast skeletal myosin inhibitor, reduced muscle damage biomarkers and stabilized function in BMD

Topic:

Clinical Trials

Poster Number: O78

Author(s):

Craig M McDonald, MD, University of California, Davis Health, Hani Kushlaf, MD, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA, Diana Castro, MD, Neurology Rare Disease Center, Denton, Texas, USA, Katherine Mathews, MD, University of Iowa, Arun Varadhachary, MD, PhD, Washington University, St. Louis, Missouri, USA, Anne M. Connolly, MD, Nationwide Children’s Hospital, Columbus, Ohio, USA, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK, Doris Leung, MD, PhD, Kennedy Krieger Institute, Jeffrey Statland, MD, University of Kansas Medical Center, Erik H Niks, MD, PhD, Leiden University Medical Center, Rosaline Quinlivan, University College London, Queen Square Institute of Neurology, London, England, UK, Varun Sreenivasan, MD, University of Colorado – Denver, Denver, Colorado, USA, Aravindhan Veerapandiyan, MD, Arkansas Children’s Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas, US, Nicholas E. Johnson, MD PhD, 3Center for Inherited Myology Research, Virginia Commonwealth University, Richmond VA 23298, USA. 4D, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, Brenda Wong, MD, UMass Medical Center, Worcester, Massachusetts, USA, Roxana Donisa Dreghici, MD, Edgewise Therapeutics, Boulder, Colorado, USA, James MacDougall, PhD, Edgewise Therapeutics, Alan Russell, PhD, Edgewise Therapeutics, Joanne Donovan, MD, PhD, Edgewise Therapeutics

Becker muscular dystrophy (BMD) is a serious, rare, neuromuscular disorder with no approved therapies. Sevasemten is an investigational, oral fast skeletal myosin inhibitor designed to protect muscle against contraction-induced damage.

CANYON (NCT05291091) is a Phase 2, double-blind, placebo-controlled study of sevasemten, assessing safety, pharmacokinetics, biomarkers of muscle damage and functional measures in adults and adolescents with Becker. Primary endpoint was change from baseline in serum creatine kinase (CK) over 6-12 months for adults. Key secondary endpoint was change from baseline in the North Star Ambulatory Assessment (NSAA) total score in adults at month 12. Other secondary endpoints include changes in circulating biomarkers and functional assessments. Forty adults and 29 adolescents with BMD were enrolled. Analysis included the adult population (n=40).

Results: Sevasemten was well-tolerated, with no new safety concerns identified in either the adult or adolescent populations. A 28% decrease from baseline CK in the sevasemten group (n=28) vs. placebo (n=12, average over months 6 through 12; p=0.02) was observed. The between-group difference for NSAA at 12 months was 1.1 points, favoring sevasemten, (p=0.16). In the sevasemten group, NSAA was stable over 12 months, consistent with previous trial observations. The decline in NSAA score in the placebo group was consistent with reported natural history studies. Fast skeletal muscle troponin I (TNNI2) showed a significant reduction of 78% compared to placebo (p<0.001), while several functional measures, including the 10-meter walk/run, 4-stair climb, and 100-meter timed test, showed trends towards improvement compared to placebo. In summary, CANYON met its primary endpoint, with rapid and sustained reductions in CK as well as TNNI2, biomarkers of muscle damage. Trends in functional improvements compared to the expected natural history were observed, albeit not significant in this study not powered for functional endpoints. A global pivotal cohort of adults with BMD, GRAND CANYON (NCT05291091), is ongoing.