LB: Long-term stabilization of function in Becker: Sevasemten prevented functional decline up to 3.5 years in MESA open-label extension

Topic:

Clinical Trials

Poster Number: 477 LBT

Author(s):

John Wing, MD, University of California - Davis, Davis, California, USA, Han Phan, MD, Rare Disease Research, Atlanta, Georgia, USA, 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, Iowa City, Iowa, USA, Arun Varadhachary, MD, PhD, Washington University School of Medicine, Anne 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, Baltimore, Maryland, USA , Jeffrey Statland, MD, University of Kansas Medical Center, Kansas City, Kansas, USA, Erik Niks, MD, PhD, Leiden University Medical Center, Leiden, Netherlands, Rosaline Quinlivan, MD, National Hospital for Neurology and Neurosurgery, 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 Johnson, MD, Virginia Commonwealth University, Richmond, Virginia, USA , Brenda Wong, MD, University of Massachusetts Medical Center, Worcester, Massachusetts, USA , James Signorovitch, PhD, Analysis Group, Inc., Boston, Massachusetts, USA , Jess Marden, BA, MPH, ScD, Analysis Group, Inc., Boston, Massachusetts, USA , Mirko Fillbrunn, PhD, Analysis Group, Inc., Boston, Massachusetts, USA , Roxana Donisa Dreghici, MD, Edgewise Therapeutics, James MacDougall, PhD, Edgewise Therapeutics, Alan Russell, PhD, Edgewise Therapeutics, Joanne Donovan, MD, PhD, Edgewise Therapeutics

Becker muscular dystrophy (BMD) is a serious neuromuscular disorder with no approved therapies. In natural history studies, patients experienced annual decreases between 1.0 -1.7 points on North Star Ambulatory Assessment (NSAA). Sevasemten is an investigational fast skeletal myosin inhibitor designed to protect muscle against contraction-induced injury and preserve function. ARCH (NCT05160415) was an open-label study in BMD adults; CANYON (NCT05291091) was a double-blind, placebo-controlled study in BMD adults and adolescents.

MESA (NCT06066580) is an open-label extension evaluating safety and efficacy in adults and adolescents previously in sevasemten trials. In MESA 99% of eligible participants continued sevasemten; this interim analysis includes participants reaching ≥12 months sevasemten. Comparison was made to a predictive model based on natural history and baseline characteristics prior to sevasemten (Niks E, et al. Neuromuscul Disord. 2025. 629P).

After 1 year of sevasemten, NSAA change at 1 year was +0.2 (95% CI: -0.4, 0.8, n=50) from baseline of 18.6. Adult CANYON participants continuing sevasemten in MESA for a total of 24 months of sevasemten (n=26) had a 0.1 point improvement from baseline. Participants initially on placebo switching to sevasemten had a 0.2 point improvement after the 1 year since initiation of sevasemten (n=11). ARCH participants continuing in MESA (n=11) also remained stable after 3.5 total years of treatment. No new safety concerns were identified.

When compared to the predictive model, CANYON and ARCH participants had NSAA scores 3.0 and 5.4 points better than the predicted -2.9 and -5.3 decline in scores expected without treatment after 24 months (1.50 points/year) and 42 months (1.54 points/year), respectively.

In summary, in participants with up to 3.5 years of sevasemten exposure, NSAA scores were stabilized with a favorable safety profile, reinforcing prior findings. Sevasemten continues to be investigated in BMD with the ongoing MESA trial and a pivotal cohort GRAND CANYON (NCT05291091).