The FDA approved mavacamten for the treatment of symptomatic, obstructive hypertrophic cardiomyopathy, the first cardiac myosin inhibitor to be permitted for use in the United States, Bristol Myers Squibb announced.

Mavacamten (Camzyos, Bristol Myers Squibb) is the first and only FDA-approved allosteric and reversible inhibitor selective for cardiac myosin that targets the underlying pathophysiology of obstructive HCM, available as 2.5 mg, 5 mg, 10 mg and 15 mg capsules. The FDA granted a breakthrough therapy designation to mavacamten for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy in July 2020.

Hypertrophic cardiomyopathy is the most common genetic heart disease, with prevalence estimates from one in 200 to one in 500. However, the true prevalence is poorly understood due to likely underdiagnosis.

“This is a first-in-class medicine specifically for patients living with symptomatic obstructive HCM,” Milind Desai, MD, MBA, director of the Hypertrophic Cardiomyopathy Center and director of clinical operations in Cleveland Clinic’s Heart Vascular & Thoracic Institute, said in the release. "With this FDA approval, U.S. cardiologists now have a new pharmacological option for eligible patients that targets the underlying pathophysiology of the disease.”

This approval is based on data from the Phase 3 EXPLORER-HCM trial. As Healio previously reported, treatment with mavacamten improved symptoms, quality of life and functional status compared with placebo in patients with symptomatic, obstructive hypertrophic cardiomyopathy. The phase 3, randomized, double-blind, placebo-controlled trial enrolled patients who had hypertrophic cardiomyopathy with a left ventricular outflow tract gradient of 50 mm Hg or greater and NYHA class II to III symptoms. The trial’s primary endpoint was a 1.5 mL/kg/min or greater increase in peak oxygen consumption (VO2) and at least one NYHA class reduction, or a 3 mL/kg/min or greater peak VO2 increase without worsening of NYHA class.

The primary endpoint was met in 36.6% of patients assigned mavacamten vs. 17.2% assigned placebo.

Treatment with mavacamten significantly improved all secondary endpoints, compared with placebo, from baseline to 30 weeks, including mean post-exercise LV outflow tract gradient, mean peak VO2, improvement in at least one NYHA class, mean change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score and mean change in Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath sub score.

“The approval of Camzyos represents a significant milestone for appropriate symptomatic obstructive HCM patients and their families, who have long awaited a new treatment option for this chronic and progressive disease,” Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, said in the release.

Considerations for use

Mavacamten reduces left ventricular ejection fraction and can cause HF due to systolic dysfunction; prescribing information for mavacamten includes a boxed warning for risk for HF. Echocardiogram assessments of LVEF are required prior to and during treatment with mavacamten and initiation of treatment in patients with LVEF less than 55% is not recommended.

Because of the risk for HF due to systolic dysfunction, mavacamten is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Camzyos REMS Program.

A second-generation cardiac myosin inhibitor for treatment of obstructive HCM, aficamten (Cytokinetics) is in development and in December received a breakthrough therapy designation from the FDA.