Hot Line 2: ODYSSEY-HCM
31 Aug 2025
Hot Line ESC Congress 2025 Mavacamten in nonobstructive hypertrophic cardiomyopathy: ODYSSEY-HCM
Yesterday, Professor Milind Desai (Cleveland Clinic - Cleveland, USA) presented results from the international phase III ODYSSEY-HCM trial designed to assess whether mavacamten improved patient-reported health status and functional capacity in patients with symptomatic nonobstructive hypertrophic cardiomyopathy (HCM).
Patients with nonobstructive HCM were enrolled with key inclusion including peak LVOT gradient <30 mmHg at rest and <50 mmHg with provocation, NYHA class II or III symptoms, Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23 CSS) ≤85, LVEF ≥60% and elevated biomarkers. In total, 580 patients were randomised to mavacamten 5 mg (with blinded dose titration as needed based on LVEF) or placebo once daily for 48 weeks. The two primary endpoints were the change from baseline to week 48 in KCCQ-23 CSS and in peak oxygen consumption.
There were no significant differences in the dual primary endpoints with mavacamten vs. placebo at week 48.
KCCQ-23 CSS increased by 13.1 in the mavacamten group and 10.4 in the placebo group (between-group difference 2.7; 95% CI –0.08 to 5.6; p=0.056). The least-squares mean increase in peak oxygen consumption was 0.52 in the mavacamten group and 0.05 in the placebo group (between group-difference 0.47 ml/kg/min; 95% CI –0.03 to 0.98; p=0.066). The secondary endpoints did not meet the requirement for further statistical testing.
Treatment-emergent adverse events resulted in permanent treatment discontinuation in 5.2% of patients with mavacamten and 2.8% with placebo. LVEF <50% occurred in 21.5% of patients with mavacamten vs. 1.7% with placebo, and all but 3 patients returned to LVEF ≥50% after study drug interruption.
Prof. Desai concluded: “Further analyses are being conducted, including two that will be presented on Sunday, to understand more about the effects of mavacamten in nonobstructive HCM and whether any patient subgroups may benefit.”
