EXPLORER-HCM Trial: Mavacamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy

EXPLORER HCM Trial mavacamten

EXPLORER HCM Trial Summary: Mavacamten is a novel cardiac-specific myosin ATPase inhibitor. It specifically reduces excessive cross-bridging with actin, which is associated with pathological hypercontractility in hypertrophic cardiomyopathy.

Clinical Question:

The EXPOLORER HCM trial evaluated the efficacy and safety of mavacamten in patients with with HCM with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II–III symptoms.

Bottom Line:

The trial had significantly positive results in favor of mavacamten. Treatment with it improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive HCM.

Trial Design:

Randomized, double-blind, placebo-controlled, phase 3 trial


In total, 251 patients were included and were randomized to receive either mavacampten (N=123) or placebo (N=128).

Inclusion Criteria:

  • ≥18 years of age with diagnosed HOCM
  • Left ventricular outflow tract [LVOT] gradient ≥50 mm Hg
  • LV ejection fraction (LVEF) ≥55%
  • New York Heart Association (NYHA) class II-III symptoms

Exclusion Criteria:

  • History of Syncope
  • Episode of Sustained VT with exercise within 6 months

Primary Outcome:

≥ 1·5 mL/kg/min increase in pVO 2 + ≥NYHA class reduction or a ≥ 3·0 mL/kg/m pVO2 increase without NYHA class worsening:

37% patients receiving mavacamten met the primary endpoint criteria compared to 17% in placebo group. diff +19·4%, 95% CI 8·7 to 30·1; p=0·0005

Key Secondary Outcomes:

  1. Post-exercise LVOT gradient:

Patients receiving mavacampten had mean of -47 mmHg change in their LVOT gradient compared to -10 mmHg in patients receiving palcebo. p<0·0001

2. Increase in pVO2 – mL/kg/min:

Up to 1.4 ml/kg/min increase was noted in pVO2 in mavacampten group compared to decrease of 0.1 ml/kg/min pVO2 in placebo group. p=0·0006

Take Home Point:

Mavacamten is the first in class myosine ATPase inhibitor that has showed efficacy in patients with obstructive HCM. Not only has it shown efficacy in treating symptoms but also improves the LVOT gradient and physiology of the heart mechanics. The EXPLORER HCM trial is one of the first trials to assess its use in patients with symptomatic HOCM.

Ref: Olivotto I et al. Lancet 2020;Aug 29