FDA Approves Mavacamten, First-in-Class Treatment for Obstructive Hypertrophic Cardiomyopathy

The cardiac myosin inhibitor is the only treatment that targets the pathophysiology of the disease, improving patient function and symptoms.

The US Food and Drug Administration (FDA) on April 28, 2022, approved mavacamten (Camzyos; Bristol Myers Squibb) for treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (obstructive HCM).

The first-in-class allosteric and reversible inhibitor selective for cardiac myosin specifically targets the underlying pathophysiology of the genetic disorder and is associated with improvement in functional capacity and symptoms, according to a statement from manufacturer Bristol Myers Squibb (BMS).

The FDA previously granted breakthrough therapy designation to mavacamten for the now-approved indication in July 2020.

Hypertrophic cardiomyopathy is considered one of the most common genetic heart diseases, and prevalence estimates range from 1 in 200 to 1 in 500. True prevalence is not well understood, however, as the condition is likely to be underdiagnosed.


The FDA based its approval of the novel treatment for adults with symptomatic New York Heart Association (NYHA) class 2-3 obstructive HCM on findings from the phase 3 EXPLORER-HCM trial, states BMS. The randomized double-blind placebo-controlled trial enrolled 251 adults with symptomatic obstructive HCM. At baseline, all had measurable left ventricular ejection fraction (LVEF) ≥55% and left ventricular outflow tract (LVOT) peak gradient ≥50% mmHg. Randomization was to a starting dose of 5 mg mavacamten or placebo once daily. The treatment period was 30 weeks with periodic adjustments to optimize patient response. The majority of all patients were on background therapy, ie, 75% on beta blockers, 17% on calcium channel blockers, according to BMS.

The EXPLORER-HCM primary endpoint was a ≥1.5 mL/kg/min increase in peak oxygen consumption (pV02) and an improvement in NYHA class by at least 1, or a ≥3 mL/kg/min pV02 increase without worsening of NYHA class.

At week 30, a greater proportion of patients treated with mavacamten met the primary endpoint vs those treated with placebo (37% vs 17%, respectively, [95% CI, 9-30; p=0.0005])

According to the press statement, patients taking mavacamten also achieved improvement in all specified secondary endpoints including mean post-exercise LVOT gradient, mean pV02, at least 1 NYHA class, and improvements on standard measures of quality of life and dyspnea.

Boxed warning, REMS

Mavacamten reduces LFEV which can lead to heart failure (HF) secondary to systolic dysfunction. Thus, the new drug’s label includes a Boxed Warning for risk of HF. Labeling also requires echocardiogram assessment of LVEF prior to and during mavacamten therapy and recommends against initiation of the drug in patients with LVEF <55%.

Given the risk of HF, according to BMS, mavacamten will be available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS) called the Camzyos REMS program.

Mavacamten will be available in 2.5 mg, 5 mg, 10 mg, and 15 mg capsules.

“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,” said 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.

“As a lead US investigator on the EXPLORER-HCM study, I’m grateful to the patients and their families whose participation in the trial played a key role in this approval.”

For additional information on mavacamten risks, dosing, etc, please see full prescribing information.