FDA Approves Mavacamten for Hypertrophic Cardiomyopathy

Now called Camzyos, the therapy is first-in-class and treats the underlying cause of the disease. It is expected to be available next week.

The FDA has approved Bristol Myers Squibb’s Camzyos (mavacamten) for the treatment of adults with obstructive hypertrophic cardiomyopathy (HCM). Camzyos is a first-in-class therapy that addresses the excessive contraction of the heart that leads to severe disease where the blood flow is obstructed. It is thought to work by decreasing the number of actin-myosin cross-bridges, which reduces the heart muscle’s ability to contract.

Camzyos is expected to available next week in 2.5 mg, 5 mg, 10 mg, and 15 mg capsules. The wholesale acquisition cost is $89,500 a year, according to Reuters.

The FDA’s original PDUFA date was January 28, 2022, but in November 2021, the regulatory agency extended the date to April 28, 2022, to review information about the proposed Risk Evaluation Mitigation Strategy (REMS).

“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, M.D., a lead investigator and medical director of the Center for Inherited Cardiac Disease and an assistant professor of medicine at the Perelman School of Medicine at the University of Pennsylvania, said in a press release.

The label of Camzyos includes a boxed warning for the risk of heart failure. Camzyos reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction. Echocardiogram assessments of LVEF are required prior to and during treatment. The therapy is not recommended for patients with LVEF <55%.

“There will be patients who will need therapy, regardless of how aggressive the REMS program is,” Arash Sadeghi, clinical pharmacist at OptumRx said in a recent interview. “The standard of care is using off-label products, such as beta blockers, calcium channel, blockers, diuretics. Those are all products that are used for other treatments in cardiology, and they have some limited data in HCM but show some relief of symptoms.”

The approval is based on data from the phase 3 EXPLORER-HCM trial, which enrolled 251 patients. Results from the trial showed that Camzyos 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 endpoints were met. The data were published in The Lancet in August 2020.

Although the therapy provides benefit, Camzyos would have to be priced below $15,000 per year to reach common thresholds for cost-effectiveness, according to the final report issued in November 2021 from the Institute for Clinical and Economic Review (ICER).

ICER reviewers also had concerns about long-term safety and an independent appraisal committee indicated that the evidence is not adequate to demonstrate a net health benefit of Camzyos added to background therapy.

“The evidence suggests that mavacamten may deliver important health benefits for patients with a lower rate of side effects than seen with some other medications for HCM, but clinical experts differ in their opinions about the long-term clinical implications of mavacamten reducing left ventricular ejection fraction in some patients. Additional safety data are needed to resolve these issues,” David Rind, M.D., ICER’s chief medical officer, said in a press release issued when the report was released.

Investigators from ICER compared Camzyos 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.