Myokardia announced positive results from the phase 2 MAVERICK-HCM clinical trial of mavacamten in patients with non-obstructive hypertrophic cardiomyopathy (HCM). The study achieved its primary objective of establishing safety and tolerability of mavacamten in non-obstructive HCM over a treatment period of 16 weeks. In addition, significant reductions in biomarkers of cardiac stress were observed in patients on treatment compared to placebo.
MAVERICK-HCM was a randomized, double-blind, placebo-controlled, concentration-guided trial and enrolled 59 patients who were randomized into one of three groups to receive once-daily doses of mavacamten or placebo. Mavacamten was well tolerated and the observed safety data were consistent with prior studies. The rate of adverse events (AEs) was greater in the mavacamten groups than the placebo group. The majority of AEs reported were mild or moderate in severity and reversible or self-resolving Meaningful reductions in biomarkers of cardiac stress were observed across both mavacamten drug concentration cohorts 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.
Based on the data, 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). For the non-obstructive indication, the company intends to consult with the U.S. FDA on potential pathways to registration and expects to provide a regulatory update in the first half of 2020. For the targeted HFpEF population, MyoKardia plans to initiate a Phase 2 study in the second quarter of 2020 in a subgroup of patients sharing many characteristics with the subgroups identified in MAVERICK-HCM.
About Non-obstructive HCM
Hypertrophic cardiomyopathy is the most common genetic form of heart disease, affecting an estimated one in every 500 people worldwide. There are two main forms of HCM, obstructive HCM and non-obstructive HCM, which often share the same underlying genetic defects in the sarcomere that results in hypercontractility. In non-obstructive HCM, the heart contracts excessively and the left ventricle becomes abnormally thick, restricting the ability of the heart to relax and fill or pump to meet the body’s needs, but no physical obstruction is present in the outflow tract of the left ventricle. Non-obstructive HCM affects an estimated one-third of all HCM patients and presents unique treatment challenges. Patients may progress to a more advanced state of disease than those with obstructive disease before being diagnosed, and there are no approved treatment options available. As non-obstructive HCM progresses, symptoms begin to resemble those of a congestive heart failure patient and heart transplantation may become the only viable treatment option.
About Mavacamten (MYK-461)
Mavacamten is a novel, oral, allosteric inhibitor of cardiac myosin. Mavacamten is intended to reduce cardiac muscle contractility by inhibiting the excessive myosin-actin cross-bridge formation that underlies the excessive contractility, left ventricular hypertrophy and reduced compliance characteristic of HCM.