FDA approves supplemental new drug application to expand Mavacamten label for hypertrophic obstructive cardiomyopathy

The FDA has approved a supplemental new drug application (sNDA) to expand the label on mavacamten (Camzyos) to include data from the Phase 3 VALOR HCM study. The study evaluated mavacamten in patients with symptomatic hypertrophic obstructive cardiomyopathy (HCM) eligible for septal reduction therapy (SRT) and with New York Heart Association (NYHA) Class 3-4 or Class 2 disease with exertional syncope or near syncope.

The label now includes information that the treatment can significantly reduce the number of symptomatic obstructive HCM patients eligible to receive SRT at 16 weeks and reduce the number of patients deciding to proceed with SRT before or after 16 weeks.

[Mavacamten] is the first and only FDA-approved cardiac myosin inhibitor that specifically targets the underlying source of the disease and is redefining the treatment landscape for NYHA class 23 symptomatic obstructive HCM, said Catherine Owen, senior vice president and general manager, US Commercial, Bristol Myers Squibb, in a press release.

Mavacamten works by reducing left ventricular outflow tract (LVOT) obstruction to improve cardiac filling pressures, which subsequently improves functional capacity and symptoms in patients with NYHA class 2-3 symptomatic obstructive HCM.

The VALOR HCM results showed that 82% of patients were no longer eligible for SRT and decided not to proceed with SRT at 16 weeks, and 18% of patients decided to proceed with SRT before week 16. 16 or at week 16 or was SRT-eligible (vs. 77% with placebo). HCM is the most common hereditary heart disease. It is caused by sarcomere dysfunction, which causes the heart muscles to thicken and reduce blood flow from the heart to the body.

Obstructive HCM can be treated with SRT, a type of catheter-based or invasive surgical procedure available at comprehensive treatment centers, said Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease, associate professor of medicine from the Perelman School of Medicine, the University of Pennsylvania, in the news release.

[But] More treatment options are needed, Owens added.

SRT can reduce the obstruction by reducing the thickness of the septal wall. Guidelines for eligibility for SRT include an LVOT gradient of 50 mmHg or greater and NYHA Class 3-4 or Class 2 with exertional syncope or near syncope.

VALOR-HCM (NCT04349072) randomized 112 eligible patients 1:1 to receive either mavacamten or placebo. The primary outcome was a composite of the proportion of patients who received SRT before or at week 16 or remained SRT-eligible at week 16, which was met in the study.

Secondary outcomes were change from baseline in post-exercise LVOT gradient, NYHA class, Kansas City Cardiomyopathy Questionnaire (KCCQ-23) clinical summary score, and cardiac biomarkers at week 16.

At 16 weeks with mavacamten regimen:

• NYHA class improved by 1 in 63% of patients (vs. 21% with placebo).
• The mean change from baseline in the KCCQ-23 Total Symptom Score (TSS) improved by 10 points (vs. 2 points with placebo).
• The mean change from baseline in KCCQ-23 Physical Limitations (PL) improved by 10 points (compared to 2 points with placebo).

Mavacamten may carry the risk of heart failure due to systolic dysfunction, so it is only available through a severely restricted program called the CAMZYOS REMS Program, which requires certification from the patient, physician, wholesaler, and pharmacy.

Mavacamten was initially approved by the FDA based on EXPLORER-HCM results. The most common adverse events in this study were dizziness and syncope (27% and 6%, respectively). No new safety signals were observed in VALOR-HCM.

Results from the Phase 3 VALOR-HCM study strengthen data from the Phase 3 EXPLORER-HCM study and further strengthen the clinical profile of mavacamten, Owen said in the press release.

Reference

Bristol Myers Squibb. US Food and Drug Administration approves addition of positive data from Phase 3 VALOR-HCM study to CAMZYOS (mavacamten) label. June 15, 2023. Accessed June 16, 2023. https://news.bms.com/news/corporate-financial/2023/US-Food-and-Drug-Administration-Approves-Addition-of-Positive-Data-from-Phase -3-VALOR-HCM-Study-to-CAMZYOS-mavacamten-Label/default.aspx