Our precision medicine platform has generated multiple programs to address a variety of disruptions in heart muscle contraction across different patient populations. We are advancing our research and development programs, each of which targets a distinct biomechanical defect that leads to either HCM or heritable DCM.
Mavacamten (formerly MYK-461) is an orally administered small molecule designed to reduce left ventricular contractility by allosterically modulating the function of cardiac myosin, the motor protein that drives heart muscle contraction. MyoKardia has evaluated mavacamten in three Phase 1 clinical trials, primarily designed to evaluate safety and tolerability of oral doses of mavacamten, as well as provide pharmacokinetic and pharmacodynamic data. In 2016, the U.S. FDA granted Orphan Drug Designation for mavacamten for the treatment of symptomatic oHCM, a subset of HCM.
MyoKardia is currently studying mavacamten in PIONEER-HCM, a Phase 2 open-label single-arm study to evaluate safety, tolerability and efficacy of MYK-461 in patients with symptomatic oHCM. The primary endpoint of PIONEER is the level of reduction in post-exercise left ventricular outflow tract (LVOT) gradient over 12 weeks of drug treatment. PIONEER is also exploring relationships among reduction in contractility and LVOT gradient, endpoints measuring functional capacity (i.e., exercise) and clinical symptoms in addition to gathering safety and tolerability data on mavacamten in an outpatient setting. In September 2017, MyoKardia presented data from the first cohort of symptomatic oHCM patients in its PIONEER-HCM Phase 2 clinical trial showing statistically significant improvements in reductions to the LVOT gradient and peak VO2, as well as clinically meaningful improvements in NYHA functional class and other parameters. The most recent data presentations from the mavacamten program may be found here.
MyoKardia is developing MYK-491 to treat dilated cardiomyopathy (DCM) by establishing normal contractility in a DCM heart. A Phase 1 clinical trial of MYK-491 in healthy volunteers is currently completing and a Phase 1 trial in patients is beginning in early 2018.
Other product candidates include HCM-2, which is being developed to lower cardiac muscle contractility in HCM patients; and LUS-1 to counteract muscle disruption resulting in impaired relaxation of the heart.