Mavacamten Allosteric modulator of cardiac myosin Treatment of hypertrophic cardiomyopathy Treatment of heart failure with preserved ejection fraction

Hypertrophic cardiomyopathy (HCM), the most common genetic cardiac disease, occurs in approximately 1 in 500 people worldwide. The current therapy for HCM does not address causal mechanisms. Mavacamten (MYK-461; MyoKardia Inc., a Bristol Myers Squibb company) is a small molecule with a potent in vitro inhibition of ATPase activity in human cardiac myofibrils. In a phase II clinical study in nonobstructive HCM (nHCM) patients, mavacamten decreased serum biomarkers of myocardial HCM, whereas in a phase III study in obstructive HCM (oHCM) patients, mavacamten improved exercise capacity, symptoms and key aspects of health status. Currently, a phase III study is assessing the long-term safety (5 years) of mavacamten in oHCM and nHCM patients, and a phase III study in oHCM patients, who are eligible for septal reduction therapy, is recruiting patients. Mavacamten, in the U.S., has been designated as an orphan drug for the treatment of symptomatic oHCM, and as a breakthrough therapy for the same indication.