Aficamten, a cardiac myosin inhibitor, increases exercise capacity and improves quality of life in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). These clinically meaningful results from the SEQUOIA-HCM trial were presented at the ESC Heart Failure Association Congress and simultaneously published in The New England Journal of Medicine.

Small-molecule, allosteric cardiac myosin inhibitors are a new class of drug and target the pathophysiology of HCM — specifically, the increased actin–myosin interacting velocity, increased force generation and increased myocardial energy consumption. In the EXPLORER-HCM trial, the first-in-class myosin inhibitor, mavacamten, was shown to reduce left ventricular outflow tract obstruction and to improve exercise capacity and symptoms compared with placebo in patients with obstructive HCM. Aficamten is an oral, reversible, small-molecule inhibitor of cardiac myosin with a similar mode of action to that of mavacamten, but a shorter half-life (allowing more rapid dose escalation and adjustment) and fewer drug–drug interactions.