Mavacamten Strikes Out in Phase III Trial of Nonobstructive HCM

In patients with nonobstructive hypertrophic cardiomyopathy (nHCM) treatment with a cardiac myosin inhibitor does not seem to yield significant improvements in quality-of-life (QoL) or oxygen consumption, an update from the phase III ODYSSEY-HCM trial has shown.

In a communication on April 14, 2025, Bristol Myers Squibb said mavacamten did not meet its dual primary endpoints of changes in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and peak oxygen consumption (pVO2) compared with placebo at 48 weeks of follow-up.

Mavacamten and another cardiac myosin inhibitor aficamten (Cytokinetics) have previously shown dramatic changes in QoL and exercise capacity in patients with obstructive HCM in trials such as VALOR-HCM, EXPLORER-HCM, SEQUOIA-HCM, and REDWOOD-HCM. In 2022, mavacamten became the first of these agents to gain US Food and Drug Administration approval for that indication.

In a press release, Bristol Myers Squibb acknowledged disappointment in the ODYSSEY-HCM results, particularly in light of the “significant need for new treatment options” in this patient population.

ODYSSEY-HCM’s primary investigator, Milind Desai, MD (Cleveland Clinic, OH), said the findings “help us understand that obstructive HCM and nonobstructive HCM are two unique diseases.” In the press release, Desai said the ODYSSEY-HCM data indicate “that we must consider new ways of thinking about potential treatment approaches for non-obstructive HCM.”

The global study enrolled 580 patients with NYHA class II or III nHCM. The investigators plan to provide more detailed results from the trial at a later date.