Mavacamten: Real-World Experience From 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program

Abstract

Background: Mavacamten is the only cardiac myosin inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy. Under the Risk Evaluation and Mitigation Strategy program for mavacamten, patients are required to be monitored for the development of systolic heart failure and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten Risk Evaluation and Mitigation Strategy database (April 28, 2022 to February 27, 2024).

Methods: Data on health care providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions before each dispense were collected.

Results: Of the 6299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were aged >60 years. Of the 5573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50%, and 71 (1.3%) experienced heart failure requiring hospitalization. On the 29 111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%), and heart failure requiring hospitalization was reported on 86 (0.3%). Of the 1929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50%, and 4 (0.2%) experienced LVEF <50% and heart failure requiring hospitalization but later resumed treatment. Of the 3228 patients initiated on 5 mg/d mavacamten and were treated for at least 6 months, 2391 (74.1%) remained at 5 or 10 mg/d. At 3 and 6 months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva left ventricular outflow tract gradient <30 mm Hg.

Conclusions: We describe the feasibility and experience of the first 22 months of the Risk Evaluation and Mitigation Strategy program for prescribing mavacamten in >6000 patients with symptomatic obstructive hypertrophic cardiomyopathy. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with heart failure requiring hospitalization.

Keywords: cardiomyopathy, hypertrophic; patient safety.

Figure 1.

Experience from prescribing mavacamten to >6000 patients with obstructive hypertrophic cardiomyopathy (HCM). HFH indicates heart failure requiring hospitalization; LVEF, left ventricular ejection fraction; PSF, Patient Status Form; and REMS, Risk Evaluation and Mitigation Strategy.

Figure 2.

Patients treated with mavacamten for ≥1 year who experienced a decrease in left ventricular ejection fraction (LVEF) to <50%, heart failure requiring hospitalization (HFH), or both. The period of data collection was extended by 2 days (April 28, 2022 and February 29, 2024) for this analysis.

Figure 3.

Dosing analysis of patients who started mavacamten at 5 mg/d and were treated for at least 6 months (n=3228). The period of data collection was extended by 2 days (April 28, 2022 and February 29, 2024) for this analysis.

Figure 4.

Valsalva left ventricular outflow tract (vLVOT) gradients for patients who began treatment with mavacamten at 5 mg/d and were treated for at least 6 months. Due to the limitations of the Risk Evaluation and Mitigation Strategy database, it is assumed that vLVOT for all patients was ≥30 mm Hg at baseline, as this is an element of the obstructive hypertrophic cardiomyopathy diagnosis. The period of data collection was extended 2 days (April 28, 2022 and February 29, 2024) for this analysis.