Sevasemten’s Effect on Cardiovascular Markers Indicate Protective Role in Becker Muscular Dystrophy

In a new analysis of the phase 2 CANYON study (NCT05291091), treatment with investigational sevasemten (Edgewise Therapeutics) led to maintained left ventricular ejection fraction (LVEF) and stable N-terminal pro–B-type natriuretic peptide (NT-proBNP) natriuretic peptides in adults with Becker muscular dystrophy (BMD). Overall, the study authors concluded that these data supported the cardiovascular safety profile of the agent, and suggest a potential cardioprotective role in this patient population.

Presented at the 2026 Muscular Dystrophy Association (MDA) Clinical & Scientific Conference, held March 8-11 in Orlando, Florida, the analysis comprised plasma samples from 28 participants on sevasemten and 12 on placebo during the 12-month CANYON trial. Led by Ben Barthel, PhD, principal scientist at Edgewise Therapeutics, data revealed that LVEF, assessed by centrally read echocardiography, correlated with NT-proBNP (r = –0.576; P <.001). For context, in adults with BMD, elevated levels of NT-proBNP can signal emerging ventricular dysfunction or worsening cardiomyopathy even before substantial declines in LVEF are detected.

In this analysis, plasma samples were analyzed by SOMAscan proteomics at baseline and at the 12-month study completion. In addition, participants were stratified into groups with normal LVEF (≥55%, n=21) and below-normal LVEF (<55%, n=14). All told, those in the below-normal LVEF group had higher baseline NT-proBNP levels, although age, baseline creatine kinase levels, and North Star Ambulatory Assessment scores were similar between groups.

For background, sevasemten is an orally administered first-in-class fast skeletal myosin inhibitor designed to protect against contraction-induced muscle damage in muscular dystrophies including Becker and Duchenne. After 12 months of sevasemten treatment, LVEF remained stable in participants with normal baseline LVEF and showed a trend toward improvement among those with below-normal LVEF. Notably, NT-proBNP was unchanged from baseline in sevasemten-treated participants and trended lower compared with those on placebo.

In BMD, cardiac involvement commonly manifests as progressive dilated cardiomyopathy, making routine cardiac monitoring essential. For context, LVEF is a key imaging measure used to assess systolic function and detect early myocardial impairment, guiding the use of cardioprotective therapies. NT-proBNP serves as a complementary biomarker reflecting ventricular wall stress and may rise with worsening cardiac dysfunction, sometimes before clear declines in LVEF are observed. Together, these measures help clinicians monitor cardiac progression and stratify risk in adults with BMD.^2,3

A previous analysis from CANYON showed that treatment with 10 mg of investigational sevasemten led to significant reductions in biomarkers associated with muscle injury in adults with BMD. After 1 month of treatment, patients receiving sevasemten demonstrated significant reductions in a panel of muscle injury proteins (P <.0001), with these reductions sustained through 6 to 12 months of treatment (P <.0001).⁴

The analysis identified several proteins as particularly responsive to treatment, including TNNI2 (P <.001), fast skeletal regulatory light chain (P <.001), and Calpain-3 (P <.001). Over the 1-year period, changes in muscle injury biomarkers among patients receiving placebo were not significantly different from those observed in natural history data (P = .01), whereas patients treated with sevasemten showed a significant reduction compared with natural history (P <.001), suggesting a potential treatment effect on underlying muscle injury pathways.

In the original analysis of CANYON, sevasemten met its primary end point, showing a 28% greater average reduction in creatine kinase levels among treated patients compared with placebo over the 6- to 12-month period (P = .02). In the original findings, investigators reported a 1.1-point advantage in NSAA scores favoring the sevasemten group among adult participants, although this difference did not reach statistical significance (P = .16).⁵

Sevasemten continued to show promising data in the open-label extension (OLE) of CANYON and ARCH, otherwise known as MESA. Data released in mid-2025 showed a 0.8-point increase in NSAA scores among patients treated with sevasemten for 18 months. Notably, there was a 0.2-point improvement observed among those who crossed over from placebo to investigational treatment in the OLE.⁶

Click here for more MDA 2026 coverage.

REFERENCES
1. Barthel B, Tran L, McDonald C, et al. LB: Effects of Sevasemten on LVEF and NT-proBNP in Adults with Becker muscular dystrophy in CANYON. Presented at: 2026 MDA Conference; March 8-11; Orlando, FL. ABSTRACT 470LB
2. Finsterer J, Stöllberger C. The heart in human dystrophinopathies. Cardiology. 2003;99(1):1–19. doi:10.1159/000068446.
3. Florian A, Rösch S, Bietenbeck M, et al. Cardiac involvement in Becker muscular dystrophy: evaluation by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2016;18:1. doi:10.1186/s12968-015-0216-0.
4. Barthel B, Improved Plasma Signature of Contraction-Induced Muscle Injury with Sevasemten in Becker Muscular Dystrophy in the CANYON Phase II Trial. Presented at: 2025 MDA Clinical & Scientific Conference. March 16-19; Dallas, TX. ABSTRACT LB432
5. Phan H, Collins S, Russell A, et al. Effects of sevasemten (EDG-5506), a fast myosin modulator, on function and biomarkers of muscle damage in adults with Becker muscular dystrophy (Becker). Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO
6. Edgewise Therapeutics Reports Positive Results on Sevasemten Program for Becker and Duchenne Muscular Dystrophies. News release. Edgewise Therapeutics. June 26, 2025. Accessed March 9, 2026. https://www.prnewswire.com/news-releases/edgewise-therapeutics-reports-positive-results-on-sevasemten-program-for-becker-and-duchenne-muscular-dystrophies-302491562.html