for Obstructive & Non-obstructive Hypertrophic Cardiomyopathy
Mavacamten for Obstructive Hypertrophic Cardiomyopathy
Mavacamten is the first therapeutic candidate in a new class of direct myosin inhibitors that targets the excessive contractility and impaired relaxation, myocardial energetics and compliance, with the intent of correcting the abnormal function of the hypertrophic cardiomyopathy (HCM) heart. MyoKardia has advanced mavacamten into multiple late-stage clinical studies looking at its potential to treat the obstructive and non-obstructive forms HCM.
Mavacamten has received breakthrough therapy and orphan drug designations for the potential treatment of symptomatic, obstructive HCM. In a randomized, controlled, pivotal Phase 3 clinical trial, known as EXPLORER-HCM, patients with symptomatic, obstructive HCM who were treated with mavacamten experienced statistically significant and clinically meaningful improvements in symptoms, functional status and key aspects of quality of life. Mavacamten treatment was also shown to bring levels of key biomarkers of cardiac wall stress and injury, closer to the normal range. Mavacamten was well tolerated, and safety results for mavcamten treatment were similar to placebo. MyoKardia plans to submit a New Drug Application (NDA) for U.S. regulatory approval in this indication in the first quarter of 2021.
MyoKardia to expand on the existing body of evidence supporting mavacamten’s use as a potential backbone therapy for HCM. The VALOR-HCM Phase 3 clinical trial designed to provide direct clinical evidence of mavacamten’s ability to mitigate the need for invasive septal reduction therapy (SRT) procedures is the first of several planned studies. VALOR is currently enrolling individuals with obstructive hypertrophic cardiomyopathy (HCM) who have been referred for SRT and are refractory to current therapeutic options, including those who have severe symptoms (NYHA Class IV).
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. The MAVA long-term extension (MAVA-LTE) study is enrolling participants from the MAVERICK-HCM and EXPLORER-HCM clinical trials.
Mavacamten for Non-Obstructive Hypertrophic Cardiomyopathy
Impaired diastolic filling is a primary driver of disease in non-obstructive HCM and certain populations of patients with HFpEF. Clinical and non-clinical studies of mavacamten have shown that mavacamten reduces cardiac muscle contractility and improves left ventricular compliance, allowing the heart to fill during diastole. In the Phase 2 MAVERICK-HCM clinical trial of symptomatic, non-obstructive HCM, mavacamten treatment over 16 weeks showed meaningful reductions in biomarkers of cardiac stress were observed and clear signals of clinical benefit were noted in a subgroup with elevated cardiac filling pressures and in a pre-specified group of patients at higher risk for morbidity and mortality..
MyoKardia plans to advance mavacamten into additional studies in defined groups of patients with non-obstructive HCM and heart failure with preserved ejection fraction (HFpEF)