The novel cardiac myosin inhibitor mavacamten may be safe and effective for patients with nonobstructive hypertrophic cardiomyopathy (HCM) and be associated with a decrease in left ventricular ejection fraction (LVEF), according to results of the phase 2 MAVERICK-HCM trial presented March 30 at ACC.20/WCC during a Featured Clinical Research session. The study has now been published in the Journal of the American College of Cardiology, along with an editorial comment.

Carolyn Ho, MD, FACC, et al., looked at safety and tolerability of mavacamten in HCM patients. The trial enrolled 59 patients who were randomly assigned a target mavacamten concentration of 200 ng/mL (n=19); target mavacamten concentration of 500 ng/mL (n=21); or a placebo (n=19).

The primary safety endpoint was the frequency and severity of treatment-emergency adverse events, adverse events of special events and serious adverse events. The researchers looked at changes from baseline to week 16 in N-terminal pro b-type natriuretic peptide (NT-proBNP); peak oxygen uptake (pVO2); NYHA functional class; echocardiographic measures of LVEF and diastolic function; and composite functional endpoint (≥1.5 mL/kg/min increase in pVO2 and ≥ 1 NYHA class improvement or ≥ 3.0 mL/kg/min increase in pVO2 without worsening in NYHA class).

At baseline, 33 patients in the mavacamten groups had NYHA Class II heart failure (HF) and seven had NYHA Class III HF, compared with 13 and six, respectively, in the placebo group. In the mavacamten groups, mean pVO2 and NT-proBNP were 20.5 mL/kg/min and 821 pg/mL, respectively, vs. 17.9 mL/kg/min and 914 pg/mL, respectively, in the placebo group. Among patients taking mavacamten, 25 were taking beta-blockers and 10 were taking calcium channel blockers at baseline vs. 12 taking beta-blockers and three taking calcium channel blockers in the placebo group. Average left ventricular ejection fraction (LVEF) was 69% in the mavacamten group vs. 66% in the placebo group.

From baseline to 24 weeks, 89.7% of patients taking mavacamten experienced at least one treatment-emergent adverse event vs. 68.4% in the placebo group. At least one serious adverse event occurred in 10.3% of patients taking mavacamten vs. 21.1% in the placebo group.

Average LVEF decreased by 4.1% among patients in the mavacamten groups, although the decrease was larger among patients whose target mavacamten concentration was 500 ng/mL. Among the placebo group, the mean LVEF reduction was 2.3%. In exploratory efficacy results, NT-ProBNP and troponin levels decreased among patients taking mavacamten, while there was little to no change in the placebo group. In addition, 35 patients taking mavacamten achieved the functional efficacy endpoint, compared with 21 in the placebo group.

According to the researchers, mavacamten is generally well tolerated in patients with nonobstructive HCM, with no increase in serious adverse events and a decrease in LVEF. The researchers note that patients with more severe disease may derive a greater benefit from treatment with mavacamten. The MAVERICK-HCM results set the groundwork for future larger-scale studies in nonobstructive HCM and potentially HF with preserved ejection fraction, the researchers conclude.

"The excitement about this small phase 2 trial relates to the notion that it introduces an entirely new class of therapeutics for a problem that has had very few options in the past," says ACC.org Editor-in-Chef Kim A. Eagle, MD, MACC.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ACC Annual Scientific Session, acc20, Myocardium, Cardiomyopathy, Hypertrophic, Heart Failure

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