Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial

RCT (n=251) of this first-in-class cardiac myosin inhibitor reported improved exercise capacity, LVOT obstruction, NYHA functional class, and health status, with 45 [37%] of 123 patients on mavacamten meeting primary endpoint versus 22 [17%] of 128 on placebo (p=0·0005).

SPS commentary:

In the study, 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 pVO2 increase without NYHA class worsening.


According to a commentary, over the past six decades, few pharmacological studies have been completed in hypertrophic cardiomyopathy. Most have been small, with the majority comprising non-randomised cohorts with no long-term follow-up. It suggest that the results of this study should be interpreted with caution in patients who are not white and in younger populations, as these groups were underrepresented in the study and should be included in future studies. In addition, the study provides no information relating to the concomitant use of disopyramide, which was included in the exclusion criteria, but is commonly used as a second-line therapy and can also prolong QT interval. Long-term follow-up data are required to assess the safety profile of mavacamten and whether its efficacy is sustained over time. It notes the long-term extension study, which will treat all patients who completed the MAVERICK-HCM7and EXPLORER-HCM6 studies with mavacamten, is in progress. It adds that should mavacamten prove to be clinically effective and safe following long-term therapy in a larger and more diverse population, it would represent a much anticipated development in the treatment of hypertrophic cardiomyopathy, and were the drug to realise its potential as a disease modifying therapy in younger individuals, it would represent a great milestone in the area of inherited cardiomyopathies.


The Lancet

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