Mavacamten improved heart function and symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM) based on results from the global, phase 3 EXPLORER-HCM trial presented at ESC Congress 2020 and simultaneously published in The Lancet.

"The results of this pivotal trial support a role for disease-specific therapy for obstructive HCM which treats the cause instead of just managing symptoms," said principal investigator Iacopo Olivotto, MD, of Careggi University Hospital, Florence, Italy.

Under the trial, a total of 251 patients received once daily mavacamten or placebo for 30 weeks. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2increase without NYHA class worsening at week 30. Secondary endpoints assessed changes in exercise capacity, symptoms, left ventricular outflow tract (LVOT) obstruction, functional status and quality of life.

Results showed 45 (36.6%) patients on mavacamten met the primary composite endpoint at week 30 compared with 22 (17.2%) patients on placebo (p=0.0005). All secondary endpoints, including post-exercise LVOT gradient and patient-reported outcomes, also demonstrated statistically significant improvements for mavacamten as compared to placebo (all p<0.0006). No significant differences in safety and tolerability were observed with mavacamten vs. placebo.

According to the authors, the findings from EXPLORER-HCM suggest "significant efficacy of the first targeted pharmacological therapy designed specifically to address the primary underlying pathophysiological basis of obstructive hypertrophic cardiomyopathy." They add that "an ongoing, long-term extension of the study will provide further evidence for clinical benefit and safety of mavacamten over five years."

"This trial is a real triumph," said ACC.org Editor in Chief Kim Eagle, MD, MACC. "First it is a brand new class of therapeutics based on elegant science. Second, the authors are to be congratulated on a superb study design in which they combined physiologic endpoints (resting and stress outflow gradients) with functional heart failure class. The striking benefits seen in both endpoints gives us confidence that the drug offers a major advance in a therapeutic area that has been in need of a breakthrough."

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ESC Congress, ESC20, Heart Failure, Cardiomyopathy, Hypertrophic

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