molecules of the month

The Cytokinetics next-generation myosin inhibitor, aficamten, is a phase II candidate for genetic hypertrophic cardiomyopathies, and is orally dosed between 5-30 mg QD. It follows BMS’s mavacamten (acquired from Myokardia in a $13.1B deal), whose NDA is under review by the FDA. This class of molecules is intended to address hypertrophic cardiomyopathy (in which thickening of the left ventricular walls limits cardiac output) by inhibiting cardiac sarcomere contractility. The molecule is reaches steady state within two weeks of dosing in a Ph. I trial rather than over six weeks for mavacamten, is safe and well-tolerated in healthy volunteers, and has low risk of DDIs with no significant cytochrome P450 induction or inhibition risk. The indoline starting point was discovered in a high-throughput phenotypic screen…