An exploratory analysis of the ODYSSEY-HCM trial has shown that mavacamten significantly reduces key cardiac biomarkers in patients with symptomatic nonobstructive hypertrophic cardiomyopathy (nHCM), a condition with no approved therapies.¹ While the main trial did not meet its primary endpoints of improving functional capacity or patient-reported health status, these biomarker findings suggest a potential physiological effect of the treatment.

Mavacamten is a first-in-class, selective, allosteric and reversible cardiac myosin inhibitor that modulates the number of myosin heads that can enter power-generating states, thus reducing the probability of force-producing systolic and residual diastolic cross-bridge formation.

The ODYSSEY-HCM trial was a randomised, placebo-controlled study evaluating the efficacy of mavacamten in adults with symptomatic nHCM.² The trial enrolled 580 patients (mean age 56 years; 45.9% women) who were randomised to receive either mavacamten or a placebo for 48 weeks. The mavacamten dose started at 5 mg daily and was titrated based on left ventricular ejection fraction. This exploratory analysis focused on the change from baseline to week 48 in two cardiac biomarkers: N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI).¹

After 48 weeks of treatment, the mavacamten group demonstrated significant reductions in both biomarkers compared to the placebo group. Patients receiving mavacamten experienced a 58% reduction in NT-proBNP (geometric mean ratio: 0.42; 95% CI: 0.37–0.47; p<0.001). Similarly, levels of hs-cTnI were reduced by 51% in the treatment arm (geometric mean ratio: 0.49; 95% CI: 0.45–0.53; p<0.001). No significant changes in either biomarker were observed in the placebo group. The study noted that these reductions occurred early in the treatment course and were sustained throughout the 48-week period.¹

The investigators concluded that, “Treatment with mavacamten for 48 weeks in nHCM patients was associated with marked biomarker improvements compared with placebo.”¹ These findings indicate a biological response to myosin inhibition in this patient population, even in the absence of observed improvements in functional or symptomatic endpoints in the primary trial analysis.

Further investigation is needed to determine the long-term clinical significance of these biomarker reductions. According to the authors, it remains to be seen “whether these changes translate into longer-term adaptive remodeling and improvements in patient-reported health status, exercise capacity, and outcomes.”¹

This study was funded by Bristol Myers Squibb.

References

1. Desai MY, Olivotto I, Abraham T, et al. Effects of Mavacamten on Cardiac Biomarkers in Nonobstructive Hypertrophic Cardiomyopathy: Insights From the ODYSSEY-HCM Trial. J Am Coll Cardiol. 2025;86(24):2418-2433. https://doi.org/10.1016/j.jacc.2025.08.017

2. Desai MY, Nissen SE, Abraham T, et al. Mavacamten in symptomatic nonobstructive hypertrophic cardiomyopathy: design, rationale, and baseline characteristics of ODYSSEY-HCM. JACC Heart Fail. 2025;13(2):358-370. https://doi.org/10.1016/j.jchf.2024.11.013

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