Aficamten (formerly CK-3773274, or CK-274) is an investigational, novel, oral, small molecule cardiac myosin inhibitor discovered by company scientists independent of its collaborations, for the potential treatment of hypertrophic cardiomyopathies (HCM). Aficamten was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
Aficamten was designed to reduce the hypercontractility associated with HCM. HCM causes the heart to thicken and stiffen, eventually limiting its ability to pump blood. This happens when myosin, a protein in the muscle responsible for converting chemical energy into the mechanical force that causes muscle contraction, is working too hard to grab or pull on actin, another protein within the sarcomere, resulting in hypercontractility, or too many hands pulling on the rope. Aficamten addresses this hypercontractility by blocking some myosins from pulling, resulting in less contraction, or fewer hands on the rope. In preclinical models, aficamten reversed and reduced thickening and stiffening of the heart.
Aficamten is the subject of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a Phase 3 randomized, placebo-controlled, double-blind, multi-center clinical trial designed to evaluate aficamten in patients with symptomatic oHCM on background medical therapy for 24 weeks. For more information on the trial, click here.