FDA Approves Updated Label for Mavacamten in Obstructive Hypertrophic Cardiomyopathy

US Food and Drug Administration logo
Credit: US Food and Drug Administration

The US Food and Drug Administration has approved a supplemental New Drug Application for mavacamten (Camzyos) to include data from the VALOR-HCM study in the prescribing information, which will now reflect the effects of the agent on need and eligibility for septal reduction therapy (SRT) in patients with obstructive hypertrophic cardiomyopathy (HCM).

Announced on June 15, 2023, the updated label, which covers the 2.5 mg, 5 mg, 10 mg, and 15 mg capsules, will reflect the reduction in guideline-based eligibility for SRT at week 16 or decision to decision to proceed with SRT prior to or at Week 16 associated with use of mavacamten in VALOR-HCM, according to a statement from Bristol Myers Squibb.

“SRT is an invasive surgical or catheter-based procedure and is typically available at comprehensive HCM treatment centers. In order to provide broader access to treatment for those patients whose obstructive HCM becomes so advanced that guidelines recommend SRT, more treatment options are needed,” said Anjali T. Owens, MD, medical director of the Center for Inherited Cardiac Disease and associate professor of Medicine at the Perelman School of Medicine at the University of Pennsylvania, and VALOR-HCM trial investigator and executive committee member. “The VALOR-HCM study supports CAMZYOS as an oral treatment for obstructive HCM patients who are recommended for SRT.”

The latest approval for mavacamten comes just more than a year after the April 2022 approval, which was based on data from the EXPLORER-HCM, made the agent the first cardiac myosin inhibitor. The April 2022 approval indicated the agent for improving functional capacity and symptoms in adult patients with symptomatic New York Heart Association (NYHA) class II-III obstructive HCM.²

The June 15, 2023 approval is based on VALOR-HCM. A randomized, doubled-blind, placebo-controlled phase 3 trial, VALOR-HCM. The trial enrolled and randomized 112 patients in a 1:1 ratio to mavacamten or placebo therapy for 16 weeks. The primary outcome of interest for the study was a composite of the proportion of patients who decided to proceed with SRT prior to or at Week 16 or who remained SRT-guideline eligible at Week 16.¹

Upon analysis, results of the trial suggested 82% of patients randomized to mavacamten met the primary endpoint. In contrast, 18% of those receiving mavacamten and 77% of those receiving placebo decided to proceed to SRT prior to or at week 16 or were SRT-eligible at week 16 (treatment different, 59% [95% confidence interval [CI], 44-74]; P < .0001). Analysis of secondary endpoints suggested use of mavacamten was associated with favorable changes from baseline to week 16 in mean post-exercise left ventricular outflow tract gradient (P < .0001), proportion with an NYHA class improvement (P < .0001), and changes in KCCQ-23 CSS scores (P < .0001).¹

Since its initial approval, the prescribing information for mavacamten has included a Boxed Warning for risk of heart failure. The warning is based on evidence suggesting use could reduce left ventricular ejection fraction and cause heart failure due to systolic dysfunction. Additionally, in their release, Bristol Myers Squibb underlined mavacamten is only available through a restricted program called the CAMZYOS REMS Program as a result of the increased risk of heart failure due to systolic dysfunction.¹

“At Bristol Myers Squibb, we are committed to delivering innovative medicines to help improve the lives of patients living with serious diseases,” said Catherine Owen, senior vice president and general manager, US Commercial, Bristol Myers Squibb.¹ “CAMZYOS 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 II–III obstructive 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 CAMZYOS. We are proud to offer this important therapy to patients.”

For more on mavacamten and the EXPLORER-HCM trial, check out this episode of Don’t Miss a Beat from June 2022 where hosts sit down with Owens to discuss the implications of the pivotal trial following the agents 2022 approval.

References:

1. Bristol Myers Squibb. U.S. Food and Drug Administration approves addition of positive data from phase 3 valor-HCM study to CAMZYOS® (mavacamten) label. News. June 15, 2023. Accessed June 15, 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.
2. Campbell P. FDA approves Mavacamten (Camzyos) for obstructive hypertrophic cardiomyopathy. HCP Live. April 28, 2022. Accessed June 15, 2023. https://www.hcplive.com/view/fda-approves-mavacamten-for-obstructive-hypertrophic-cardiomyopathy.