ODYSSEY-HCM: Mavacamten misses primary endpoint in non-obstructive HCM 

Mavacamten did not improve exercise capacity or patient-reported symptom scores in patients with non-obstructive hypertrophic cardiomyopathy (HCM), according to results of the phase 3 ODYSSEY-HCM trial.  

The ODYSSEY-HCM trial (NCT05582395) randomised 580 patients with symptomatic non-obstructive HCM 1:1 to the first-in-class cardiac myosin inhibitor mavacamten or placebo. The dual primary endpoints were the changes from baseline to week 48 in peak oxygen consumption (pVO2) and Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 clinical symptom score. Dr Milind Desai (Cleveland Clinic, OH, USA) presented the findings [1].

The primary endpoints were not met. Change from baseline to week 48 in peak VO2 was 0.05 ml/kg/min for placebo and 0.52 ml/kg/min for mavacamten (delta 0.47; 95% CI -0.03 +0.98; P=0.066). For the KCCQ clinical symptom score, the change was 10.4 points for placebo and 13.1 points for mavacamten, reflecting a non-significant difference of 2.7 points (95% CI -0.1 to +5.6; P=0.056).

Dr Desai noted that treatment-emergent adverse events leading to drug discontinuation occurred in 5.2% of the patients on mavacamten and in 2.8% on placebo. Congestive heart failure (6.6% vs 1.7%) and atrial tachyarrhythmias (4.2% vs 3.4%) were reported slightly more often with mavacamten. “Reversible left ventricular systolic dysfunction occurred in approximately 1 in 5 patients,” said Dr Desai. “This was likely driven by the dose titration strategies in non-obstructive HCM and advanced disease burden.”

Altogether, treatment with mavacamten did not result in significant improvements in exercise capacity or KCCQ clinical symptom scores in symptomatic non-obstructive HCM. “Ongoing research in imaging, biomarkers, and detailed responder analyses will further explore potential benefits of mavacamten in selected patient subgroups,” Dr Desai concluded.

1. Desai MY, et al. Mavacamten in symptomatic non-obstructive cardiomyopathy: primary results of the ODYSSEY-HCM trial. Hotline 2, ESC Congress 2025, 29 August – 1 September, Madrid, Spain.

Medical writing support was provided by Robert van den Heuvel.

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Posted on 1 September 20257 November 2025