Results from the multicentre, phase 3 EXPLORER­HCM trial highlight the benefits of a disease-specific treatment for patients with obstructive hypertrophic cardiomyopathy. Mavacamten, a first-in-class cardiac myosin inhibitor, improved left arterial volume index, lateral E/e’, septal E/e’, and left ventricular (LV) mass index in this patient population [1,2].

Dr. Sheila Hegde (Brigham and Women’s Hospital, USA) presented the results of the randomized, double-blind, placebo-controlled EXPLORER­-HCM trial. This study evaluated the efficacy and safety of mavacamten in patients with hypertrophic cardiomyopathy with an LVOT gradient of ≥50 mmHg and NYHA class II-III symptoms. Participants from 68 centers in 13 countries were randomly assigned to mavacamten (n=123) or placebo (n=128). The primary endpoint was a composite functional endpoint designed to specifically demonstrate benefit both in symptoms and function, namely a ≥1.5 mL/kg per min increase in peak oxygen consumption (pVO2) and at least 1 NYHA class reduction or a ≥3.0 mL/kg per min pVO2 increase without NYHA class worsening.

The results showed that 37% of patients in the mavacamten group versus 17% in the placebo group met the primary endpoint after 30 weeks (difference +19.4; 95% CI 8.7-30.1; P=0.0005). Furthermore, 30-week treatment with mavacamten led to significant reductions in left arterial volume index, lateral E/e’, septal E/e’, and LV mass index compared with placebo. Significantly more patients treated with mavacamten than placebo achieved resolution of mitral valve systolic anterior motion and mitral regurgitation (80.9% vs 34.0%, and 9.0% vs 0.0%, respectively). Safety was similar between groups, and treatment-emergent adverse events were generally mild.

In this first randomized phase 3 trial with positive results in patients with obstructive hypertrophic cardiomyopathy, mavacamten not only improved functional capacity and LVOT gradient but also symptoms and key aspects of health status (secondary endpoints) as well as key pathophysiological processes. These results highlight the benefits of disease­specific treatment in hypertrophic cardiomyopathy.

  1. Hegde S, et al. Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study. Abstract P1732, Virtual AHA Scientific Sessions 2020, 13-17 Nov.
  2. Olivotto I, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet 2020, August 29.