Aficamten in the treatment of obstructive hypertrophic cardiomyopathy

Aficamten is a novel cardiac myosin inhibitor that has completed a Phase III trial for the treatment of obstructive hypertrophic cardiomyopathy (HCM). Aficamten was developed to optimize pharmacokinetic properties and clinical tolerability relative to its predecessor, mavacamten. Mechanistically, aficamten decreases myocardial contractility by way of reducing cardiac myosin ATPase activity and the number of active actin-myosin cross bridges during the cardiac cycle. Clinically, aficamten improves cardiac hemodynamics and biomarker profiles while promoting favorable cardiac remodeling, augmenting exercise tolerance and improving overall health status. Observed systolic dysfunction was infrequent, mild, reversible, and not associated with serious adverse events. Collectively, the available data suggests that aficamten is a well-tolerated drug that shows strong clinical efficacy across a wide array of clinical parameters. In this review, we provide a comprehensive description of the pharmacology, clinical efficacy, and tolerability of aficamten.