Mavacamten-Evidence in Obstructive vs. Nonobstructive HCM
Mavacamten-Evidence in Obstructive vs. Nonobstructive HCM
Source (ESC 2025, Madrid): NEJM 2025 – ODYSSEY-HCM. JACC 2025 – COLLIGO-HCM
Keynotes:
1. Proven efficacy in obstructive HCM:
• The EXPLORER-HCM trial (NEJM 2020) demonstrated that mavacamten significantly improved exercise capacity, symptoms, and quality of life, while reducing LV outflow tract gradients in patients with symptomatic obstructive HCM.
• These results led to FDA approval in 2022 (Camzyos, Bristol Myers Squibb) as the first pharmacologic therapy for symptomatic obstructive HCM. (NEJM 2020)
2. Lack of benefit in nonobstructive HCM:
• In the ODYSSEY-HCM Phase III trial (NEJM, Sept 2025), mavacamten did not outperform placebo in improving peak oxygen uptake or KCCQ-CSS symptom scores over 48 weeks in patients with symptomatic nonobstructive HCM.
• Participants had resting LVOT gradients < 30 mm Hg (< 50 mm Hg with provocation), NYHA class II–III, and LVEF ≥ 60%.
• Authors suggested that in nonobstructive disease, symptoms may result more from diastolic dysfunction, ischemia, ventricular stiffness, and altered energetics, conditions less responsive to myosin inhibition.
• Commentary highlighted that this negative outcome confirms that nonobstructive HCM is not simply a mirror image of obstructive HCM, stressing the need for novel therapeutic approaches.
NEJM 2025 – ODYSSEY-HCM (negative trial results) — http://www.nejm.org/doi/full/10.1056/NEJMoa2505927.
