Mavacamten

Mavacamten is a first-in-class small molecule therapeutic that reversibly binds to myosin to directly target the excess contractility and impaired relaxation underlying hypertrophic cardiomyopathy, or HCM.
MyoKardia has advanced mavacamten into multiple late-stage clinical studies looking at its potential to treat the obstructive and non-obstructive forms of HCM. Our pivotal Phase 3 EXPLORER-HCM clinical trial of mavacamten is designed to demonstrate improvements in symptoms and function in patients with symptomatic obstructive HCM. We expect to report data from the EXPLORER-HCM clinical trial in the second quarter of 2020.

Mavacamten is also being studied in a Phase 2 clinical trial, known as MAVERICK-HCM, in symptomatic non-obstructive HCM patients. The MAVERICK-HCM trial is primarily a dose-ranging study to assess safety and tolerability in the non-obstructive HCM population. Topline data from the Phase 2 MAVERICK-HCM clinical trial is anticipated in the fourth quarter of 2019.

Both the EXPLORER-HCM and MAVERICK-HCM clinical trials were guided and informed by MyoKardia’s Phase 2 PIONEER-HCM trial of mavacamten in patients with symptomatic, obstructive HCM. In the open-label Phase 2 PIONEER-HCM dose-ranging study, treatment with mavacamten for twelve weeks resulted in significant improvements across the primary and secondary endpoints measured. Among the most noteworthy findings were that mavacamten could be dosed to reduce left ventricular outflow tract (LVOT) gradient below the guideline-based definition for obstruction. Along with LVOT gradient reductions, patients experienced improvements in New York Heart Association (NYHA) functional classification and exercise capacity as measured by peak VO2 levels. Reductions in shortness of breath and in levels of NT-proBNP, a well-established marker of ventricular wall stress, were also observed.

Importantly, mavacamten has been well tolerated. We are conducting two long-term extension studies to evaluate safety and activity with chronic dosing of mavacamten. The PIONEER open-label extension (PIONEER-OLE) enrolled patients who participated in MyoKardia’s Phase 2 PIONEER-HCM clinical trial. Twelve- and twenty-four-week data from PIONEER-OLE show that mavacamten could be dosed on an individualized basis to eliminate LVOT gradient while maintaining ejection fractions above the normal range. The MAVA long-term extension (MAVA-LTE) study is enrolling participants from the MAVERICK-HCM and EXPLORER-HCM clinical trials.