MyoKardia Begins Dosing in Phase 2 MAVERICK-HCM Clinical Trial of Mavacamten

MyoKardia, Inc. announced that the first patient has been dosed in the company’s Phase 2 MAVERICK-HCM clinical trial. MAVERICK-HCM is the first clinical trial of mavacamten in non-obstructive HCM, expanding its potential use to an additional sub-type of HCM beyond the obstructed form of the disease.

The two sub-types of HCM, obstructive and non-obstructive, share the same underlying genetic defects in the sarcomere that results in hypercontractility. In nHCM, the heart contracts excessively, but no physical obstruction is present in the outflow tract of the left ventricle. As a result of the hypercontractility, the left ventricle becomes abnormally thick and fibrotic, which prevents the heart from being able to relax and fill with blood normally. Mavacamten acts by inhibiting the excessive myosin-actin crossbridge formation that underlies HCM’s characteristic excessive contractility, left ventricular hypertrophy and reduced ventricular compliance.

“Patients with nHCM tend to get diagnosed once their disease is quite advanced, by which time they are already experiencing symptoms that force them to restrict their regular everyday activities. With no approved therapeutic interventions available, current treatment options are limited to off-label medications aimed at symptom relief, or heart transplant,” said Dr. Stephen Heitner, cardiologist at the Oregon Health & Science University Knight Cardiovascular Institute and principal investigator for the MAVERICK-HCM clinical trial. “The prospect of a pill that could reduce the hypercontractility that underpins this disease and improve patients’ ability to function could truly change the nHCM treatment paradigm. I am excited to be part of this study and look forward to evaluating mavacamten in this population.”

The Phase 2 MAVERICK-HCM trial is a double-blind, placebo-controlled study designed to assess the safety and tolerability of a 16-week treatment course of mavacamten. Secondary endpoints from the trial will assess the effect of mavacamten on exercise capacity as measured by peak oxygen uptake (peak VO2), changes in NYHA functional classification, diastolic and systolic function as measured by echocardiography, symptoms and quality of life measures, NT pro-BNP levels and patient activity as measured by a wrist-worn accelerometer.

The trial is expected to enroll approximately 60 patients with nHCM and preserved left ventricular ejection fraction. Patients will be randomized evenly into three groups to receive a once-daily dose of mavacamten targeting one of two plasma concentration levels of drug or placebo. At Week 4, pharmacokinetics (PK) will be assessed in each patient and the dose will be adjusted at Week 6 in order to achieve the target drug concentration. Patients will be allowed to maintain background medications (beta blockers or calcium channel blockers) for the duration of the MAVERICK-HCM Phase 2 trial. In addition to the 16-week treatment period, patients will participate in a screening period of up to four weeks and will be monitored for an additional eight weeks after discontinuation of mavacamten. Topline data from the MAVERICK-HCM trial are anticipated in the second half of 2019.

“We are pleased to be advancing mavacamten into a second potential indication where we have the opportunity to evaluate its potential in non-obstructive HCM. Based on the positive results from the Phase 2 PIONEER-HCM study in oHCM, we have reason to believe that its mechanism of action may also be of benefit to nHCM patients,” said Marc Semigran, M.D., Chief Medical Officer of MyoKardia. “In addition to targeting the hypercontractility characteristic of HCM, we have seen preclinical and clinical evidence that mavacamten may facilitate increased ventricular compliance. The MAVERICK study promises to provide greater insights into mavacamten’s potential effect on diastolic function.”

Mavacamten has been evaluated across six clinical trials and 175 participants to date, and has shown to be generally well-tolerated. Positive results from the Phase 2 PIONEER-HCM clinical trial in patients with oHCM demonstrated clinical improvement in symptoms (e.g., NYHA functional class) and exercise capacity (peak VO2). The Phase 3 EXPLORER-HCM pivotal trial of mavacamten in oHCM is expected to begin patient dosing in the second quarter of 2018.