FDA Approves Supplemental New Drug Application To Expand Mavacamten Label for Obstructive Hypertrophic Cardiomyopathy

The FDA approved a supplemental New Drug Application (sNDA) to expand the label on mavacamten (Camzyos) to include data from the phase 3 VALOR HCM trial. The study evaluated mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) who are eligible to receive septal reduction therapy (SRT) and have New York Heart Association (NYHA) class 3-4 disease, or class 2 with exertional syncope or near syncope.

The label now includes information that treatment can significantly reduce the number of patients with symptomatic obstructive HCM who are eligible to receive SRT at 16 weeks and reduce the number of patients who decide to proceed with SRT prior to or at 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 symptomatic NYHA class 2–3 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 symptomatic NYHA class 2-3 obstructive HCM.

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

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

“[But] more treatment options are needed,” Owens added.

SRT can reduce obstruction by reducing thickness of the septal wall. Guidelines for SRT-eligibility include an LVOT gradient of 50 mmHg or higher, 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 mavacamten or placebo. The primary outcome was a composite of the proportion of patients who received SRT prior to or at week 16 or remained SRT-guideline eligible at week 16, which was achieved in thr trial.

Secondary outcomes were change from baseline on post-exercise LVOT gradient, NYHA class, Kansas City Cardiomyopathy Questionnaire (KCCQ-23) Clinical Summary Score, and cardiac biomarkers at week 16.

At 16 weeks on mavacamten regimen:

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

Mavacamten can cause risk of heart failure due to systolic disfunction, thus it is only available through a heavily restricted program called the CAMZYOS REMS Program, which requires certification by the patient, physician, wholesaler, and pharmacy.

Mavacamten was initially approved by the FDA based on the results of EXPLORER-HCM. The most common adverse events from 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 reinforce the data from the phase 3 EXPLORER-HCM trial and further strengthen the clinical profile of mavacamten,” Owen said in the press release.

Reference

Bristol Myers Squibb. U.S. Food and Drug Administration Approves Addition of Positive Data from Phase 3 VALOR-HCM Study to CAMZYOS® (mavacamten) Label. June 15, 2023. Accessed on June 16, 2023. https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Approves-Addition-of-Positive-Data-from-Phase-3-VALOR-HCM-Study-to-CAMZYOS-mavacamten-Label/default.aspx