First Patient with Non-Obstructive HCM Dosed in Phase 2 Study

The first patient has been dosed in MyoKardia’s Phase 2 MAVERICK-HCM clinical trial of mavacamten in symptomatic non-obstructive hypertrophic cardiomyopathy (HCM) patients.

The study is the first of mavacamten in non-obstructive HCM, expanding its potential use to an additional subtype of the condition beyond its obstructed form. Both the obstructive and non-obstructive variations of the disease share the same underlying genetic defects in the sarcomere, resulting in hypercontractility.

To date, mavacamten has been evaluated across 6 clinical trials and 175 participants to date, and has exhibited to be generally well-tolerated. Positive results from the Phase 2 PIONEER-HCM clinical trial in patients with obstructed HCM demonstrated a clinical improvement in symptomology and exercise capacity.

In non-obstructive HCM, the heart contracts excessively, but no physical obstruction is present in the outflow tract of the left ventricle, leading it to become abnormally thick and fibrotic. Mavacamten has been developed to inhibit the excessive myosin-actin cross bridge formation that underlies HCM’s characteristic excessive contractility, left ventricular hypertrophy and reduced ventricular compliance. The drug allows the heart to continue operating in a relaxed fashion and fill with blood in the typical fashion.

Oftentimes, patients with non-obstructive HCM don’t receive the proper diagnosis until the disease is quite advanced, by which time they are likely 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 in a press release. “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.”

The Phase 2 MAVERICK-HCM trial is expected to enroll approximately 60 patients with non-obstructive HCM and preserved left ventricular ejection fraction and the safety and tolerability of a 16-week treatment course of mavacamten is serving as the primary endpoint.

Patients will be randomized evenly into 3 groups to receive a once-daily dose of mavacamten targeting 1 of 2 plasma concentration levels of drug or placebo.

Secondary endpoints from the trial will evaluate the effect of mavacamten on exercise capacity as measured by peak oxygen uptake (peak VO2), changes in the NYHA functional classification, diastolic and systolic function as measured by echocardiography, symptoms, and quality of life (QOL) measures, NT pro-BNP levels and patient activity as measured by a wrist-worn accelerometer.

At Week 4, pharmacokinetics (PK) will be assessed in each patient and the dose will be adjusted at Week 6 to achieve the target drug concentration. Patients will be permitted to maintain background medications, like beta blockers or calcium channel blockers, for the duration of the trial. In addition to the 16-week treatment period, patients will participate in a screening period of up to 4 weeks and will be monitored for an additional 8 weeks after discontinuation of mavacamten.

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