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Mavacamten effective in obstructive hypertrophic cardiomyopathy

Presented by
Dr Sheila Hegde, Brigham and Women’s Hospital, USA
AHA 2020
Results from the multicentre, phase 3 EXPLORER-HCM trial highlight the benefits of a disease-specific treatment for patients with obstructive hypertrophic cardiomyopathy. Mavacamten, a first-in-class cardiac myosin inhibitor, improved exercise capacity, left ventricular outflow tract (LVOT) obstruction, NYHA functional class, and health status in this patient population [1,2].

Dr Sheila Hegde (Brigham and Women's Hospital, USA) presented the results of the randomised, double-blind, placebo-controlled phase 3 EXPLORER-HCM trial (NCT03470545). This study evaluated the efficacy and safety of mavacamten in patients with hypertrophic cardiomyopathy with a LVOT gradient of ≥50 mmHg and NYHA class II-III symptoms. Participants from 68 centres in 13 countries were randomly assigned to mavacamten 5 mg daily (n=123) or placebo (n=128) for 30 weeks. 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. Mean patient age was 59 years; 46% were female.

The primary endpoint was met by 37% of patients in the mavacamten group versus 17% in the placebo group (difference 19.4; 95% CI 8.7–30.1; P=0.0005). Post-exercise LVOT gradient change was -47 mmHg and -10 mmHg in the mavacamten and placebo groups, respectively (P<0.0001). The pVO2 change was 1.4 mL/kg/min and -0.1 mL/kg/min (P=0.0006). Improvement by at least one NYHA class occurred in 34% more patients in the mavacamten group: 80 of 123 patients in the mavacamten group versus 40 of 128 patients in the placebo group (95% CI 22.2–45.4; P<0.0001).

A cardiac magnetic resonance (CMR) substudy analysis revealed a change in LV mass index of -17.4 g/m2 and -1.6 g/m2 in the mavacamten and placebo group, respectively (P<0.0001). Change in LVEF was -6.6% versus -0.3% (P=0.0025). Safety was similar between groups, and treatment-emergent adverse events were generally mild.

Dr Hegde concluded that in this first randomised 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 as well as key pathophysiological processes. These results highlight the benefits of disease-specific treatment for this condition.

    1. Hegde SM, et al. Mavacamten Favorably Impacts Key Pathophysiologic Processes in Obstructive Hypertrophic Cardiomyopathy: Results From the EXPLORER-HCM Study. Abstract P1732, AHA Scientific Sessions 2020, 13–17 Nov.
    2. Olivotto I, et al. Lancet 2020;396(10253):759–769.


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