Aficamten—A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy

Abstract

Hypertrophic cardiomyopathy is an under-recognized disease with a genetic component that results in abnormal and often asymmetric thickening of the left ventricle in addition to decreased compliance and progressive fibrosis of the myocardium. It further poses significant complications related to dynamic left ventricular outflow obstruction over time in a significant majority. The medical management of obstructive hypertrophic cardiomyopathy has evolved over the decades as our understanding has grown. Traditionally, the mainstay in management has included the use of various negative inotropic agents. In contrast, the cardiac myosin inhibitors, aficamten and mavacamten, are novel therapies targeting cardiac contractility at the sarcomere level that have demonstrated improvement in clinical outcomes for patients, and mavacamten (Bristol Myers Squibb, Inc.) has now been approved by the Food and Drug Administration for the treatment of symptomatic obstructive HCM. Aficamten (Cytokinetics, Inc.) is the second in class cardiac myosin inhibitor that is currently being evaluated in ongoing phase III clinical trials, and is the subject of this review.