Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy: Phase 3 Results

Cardiomyopathy – diagnosis written on a white piece of paper. Syringe and vaccine with drugs.
Mavacamten was associated with improvements in patients with obstructive hypertrophic cardiomyopathy.

In patients with obstructive hypertrophic cardiomyopathy, treatment with mavacamten was associated with improvements in exercise capacity, left ventricular outflow tract (LVOT) obstruction, New York Heart Association (NYHA) functional class, and health status, according to a study published in the Lancet.

Mavacamten is a selective allosteric inhibitor of cardiac myosin ATPase. The drug candidate was developed to target the underlying pathophysiology of hypertrophic cardiomyopathy by diminishing cardiac contractility and improving myocardial energetics.

In this phase 3 EXPLORER-HCM trial, patients with hypertrophic cardiomyopathy were recruited from 68 clinical cardiovascular centers in 13 countries. All participants had an LVOT gradient ≥50 mmHg and a New York Heart Association (NYHA) functional class of 2 to 3, and were randomly assigned to receive mavacamten (n=123) or placebo (n=128) for 30 weeks. Individualized doses of mavacamten were 2.5 mg, 5 mg, 10 mg, and 15 mg to achieve a target reduction in LVOT gradient <30 mmHg and a mavacamten plasma concentration between 350 ng/mL and 700 ng/mL.

The study’s primary endpoint was an increase in peak oxygen consumption (pVO2) ≥1.5 mL/kg/minute and reduction ≥1 in NYHA class or an increase in pVO2 ≥3.0 mL/kg/minute without worsening of NYHA class. Other endpoints included changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB).

A greater percentage of participants receiving mavacamten vs placebo met the primary endpoint (37% vs 17%, respectively; difference, +19.4%; 95% CI, 8.7-30.1; P =.0005). Greater reductions in post-exercise LVOT gradient were observed in the mavacamten vs placebo group (difference, –36 mm Hg; 95% CI, –43.2 to –28.1; P <.0001).

In addition, treatment with mavacamten vs placebo was associated with a greater increase in pVO2 (difference, +1.4 mL/kg/minute; 95% CI, 0.6-2.1; P =.0006) and greater improvements in KCCQ-CSS (difference, +9.1; 95% CI, 5.5-12.7; P <.0001) and HCMSQ-SoB (difference, –1.8; 95% CI, –2.4 to –1.2; P <.0001) scores.

A greater percentage of patients treated with mavacamten vs placebo experienced a ≥1 improvement in NYHA class (65% vs 31%, respectively; 95% CI, 22.2-45.4; P <.0001). No differences were found between the 2 treatment groups in terms of safety and tolerability outcomes. Approximately 88% of patients in the mavacamten arm and 79% of patients in the placebo group experienced ≥1 treatment-emergent event, most of which were mild in severity. There was 1 sudden death in the placebo group.

The exclusion criteria of this study, which were applied to patients treated with disopyramide and those with severe symptoms, may limit the generalizability of the findings.

 “The results of this pivotal trial highlight the benefits of disease­specific treatment in hypertrophic cardiomyopathy,” noted the study authors.

Disclosure: This clinical trial was supported by MyoKardia. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Olivotto I, Oreziak A, Barriales-Villa R, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759-769. doi:10.1016/S0140-6736(20)31792-X