Novel Therapy for Hypertrophic Cardiomyopathy

Mavacamten is now available on the Pharmaceutical Benefits Scheme (PBS) to treat symptomatic obstructive hypertrophic cardiomyopathy. Mavacamten is a novel drug that acts as a selective and reversible inhibitor of cardiac myosin. It reduces the probability of myosin being in the active state, thereby decreasing cardiac hypercontractility and its associated adverse effects.

The pivotal EXPLORER-HCM study investigated the efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy. This randomised, placebo-controlled trial found that mavacamten improved exercise capacity, left ventricular outflow tract (LVOT) obstruction, New York Heart Association (NYHA) functional class, and health status.

The recommended starting dose is 5mg daily, with careful dose titration required according to the LVOT gradient. Mavacamten treatment should not be initiated in patients with a left ventricular ejection fraction (LVEF) <55%, and treatment should be interrupted if the LVEF is <50% at any clinical visit.

The primary method of clearance from the plasma is hepatic metabolism, which leads to some clinically significant drug interactions. Mavacamten is contraindicated with moderate to strong CYP2C19 inhibitors (e.g. fluoxetine), strong CYP3A4 inhibitors (e.g. itraconazole), and moderate to strong inducers of CYP2C19 or CYP3A4 (e.g. rifampicin).