ICER Releases Draft Report on Mavacamten in Cardiomyopathy

A potential first-in-class therapy now being reviewed by the FDA to treat hypertrophic cardiomyopathy, a serious disease that can cause sudden death, has the potential to generate higher amounts of quality-adjusted life-years (QALY) but with a incremental cost-effectiveness ratio that could be above standard thresholds, according to a new draft report from the Institute for Clinical and Economic Review (ICER) in Boston.

At a placeholder price of $75,000 per year for mavacamten used along with standard first-line treatment for symptomatic obstructive hypertrophic cardiomyopathy was above the threshold of $150,000 per QALY.

Hypertrophic cardiomyopathy is a chronic, progressive disease in which excessive contraction of the heart muscle can lead to the development of debilitating symptoms and cardiac dysfunction.

In patients with hypertrophic cardiomyopathy, the heart muscle becomes abnormally thick, making it harder for the heart to pump blood. The thickened heart muscle can cause shortness of breath, chest pain, or problems in the heart’s electrical system, resulting in life-threatening arrhythmias or sudden death, according to the Mayo Clinic.

In obstructive disease, the thickened heart wall can block or reduce the flow of blood from the left ventricle to the aorta.

It’s estimated that 1 in every 500 people have hypertrophic cardiomyopathy, but a large percentage of patients are undiagnosed, according to the American Heart Association. Of those diagnosed, two-thirds have the obstructive form of the disease.

In March 2021, the FDA accepted Bristol Myers Squibb’s new drug application (NDA) for mavacamten, an investigational, novel, oral medication for patients with symptomatic obstructive hypertrophic cardiomyopathy. The agency’s PDUFA target date is January 28, 2022.

The NDA is based on data from the EXPLORER-HCM phase 3 clinical trial, which enrolled 251 patients. Results from the trial showed that mavacamten demonstrated a robust treatment effect, with clinically meaningful improvements in symptoms, functional status, and quality of life, as well as the ability to relieve left ventricular obstruction. Investigators found that all primary and secondary end points were met.

The data were presented at the European Society of Cardiology 2020 Congress and published simultaneously last year in The Lancet. Investigators at the Congress said mavacamten offers the hope of avoiding surgery, as well as the potential to cure the disease.

Investigators from ICER compared mavacamten with Pfizer’s Norpace (disopyramide), which is an anti-arrhythmic drug approved for the treatment of arrhythmia, although it is used with patients who have obstructive hypertrophic cardiomyopathy who are not controlled with beta blockers or the calcium channel blocker verapamil.

Norpace has similar benefits to mavacamten, ICER said, but Norpace has been known to cause side effects, and the long-acting formulation suffers from shortages.

According to the ICER review, mavacamten results in an incremental cost per QALY that is well above standard thresholds. The incremental cost per QALY is even higher when comparing mavacamten with disopyramide is even higher, but ICER investigators said that cost-effectiveness will depend on the actual cost of mavacamten.