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Mavacamten benefits patients with obstructive hypertrophic cardiomyopathy

Mavacamten treatment may reduce left ventricular outflow tract gradient and improve exercise capacity in patients with obstructive hypertrophic cardiomyopathy, according to data from the phase 2 PIONEER-HCM study.

“Mavacamten is a first-in-class, cardiac specific, small-molecule allosteric modulator of beta-cardiac mysin that reversibly inhibits its binding to actin,” Stephen B. Heitner, MD, of the Knight Cardiovascular Institute at Oregon Health & Science University, and colleagues wrote. “It is intended to reduce resting and dynamic [left ventricular outflow tract (LVOT)] obstruction in patients with [obstructive hypertrophic cardiomyopathy (HCM)] by normalizing the function of myosin protein in hypercontractile hearts, regardless of the presence of a sarcomeric gene mutation.”

Researchers conducted the study in two sequential cohorts, each with 12 weeks of once-daily mavacamten followed by a 4-week post-treatment phase. The study included 21 symptomatic patients with obstructive HCM. Cohort A was designed for proof-of-concept. Patients received 10 mg to 20 mg mavacamten per day without background medications. In cohort B, patients received 2 mg to 5 mg per day, and beta blockers were allowed. Patients were assessed at weekly visits for 8 weeks, at an end-of-treatment visit at 12 weeks, and an end-of-study visit at week 16.

Mavacamten reduced mean post-exercise LVOT gradient from 103 mm Hg at the baseline to 19 mm Hg at 12 weeks (mean change, –89.5 mm Hg; 95% CI, –138.3 to –40.7), and reduced resting left ventricular ejection fraction (LVEF) in cohort A (mean change, –15%; 95% CI, –23 to –6). In cohort B, the mean post-exercise LVOT decreased from 86 mm Hg to 64 mm Hg (mean change, –25; 95% CI, –47.1 to –3), and the mean change in resting LVEF was –6% (95% CI, –10 to –1).

Researchers found that mavacamten was well tolerated and had mostly mild (80%), moderate (19%) and unrelated (79%) adverse events. Decreased LVEF at higher plasma concentrations and atrial fibrillation were the most common adverse events related to mavacamten.

“If confirmed in larger studies, these data suggest a potential role for mavacamten in the treatment of [obstructive] HCM,” Heitner and colleagues wrote. – by Erin Michael

Disclosures: Heitner reports a grant from MyoKardia during the conduct of the study, other support from MyoKardia and Cytokinetics outside of the submitted work, and service on the steering committee for the EXPLORER trial for MyoKardia. Please see study for all other authors’ relevant financial disclosures.