Post-marketing safety signal profile of mavacamten in the FDA adverse event reporting system (FAERS): a disproportionality analysis.

BACKGROUND: Mavacamten is a first-in-class cardiac myosin inhibitor approved for symptomatic obstructive hypertrophic cardiomyopathy; however, its risk of reduced left ventricular ejection fraction and systolic heart failure warrants post-marketing safety evaluation. METHODS: FAERS quarterly open data from 2022 Q2 to 2025 Q2 (13 quarters) were retrospectively analyzed. After global deduplication, mavacamten reports were identified using "MAVACAMTEN" or "CAMZYOS" as primary or secondary suspect drugs. Disproportionality was assessed by the reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayes geometric mean (EBGM). A positive primary signal required at least 3 reports, a lower bound of the ROR 95% confidence interval (CI) greater than 1, and IC025 greater than 0; PRR and EBGM served as consistency measures only. Sensitivity analyses included count-threshold analyses and an exploratory covariate-adjusted ROR (aROR) analysis. RESULTS: Among 4,514,490 deduplicated FAERS cases, 2,933 mavacamten-associated reports were identified, containing 955 unique preferred terms (PTs). Eighty PTs met the primary signal criterion (68 clinical, 9 administrative/product-use, 3 ambiguous); 45 were concordant across all four algorithms. Ejection fraction decreased was a prominent labeled cardiac safety signal (a = 99; ROR 47.08, 95% CI 38.42-57.69; aROR 54.74, 95% CI 44.53-67.30), together with atrial fibrillation (a = 205; ROR 17.63, 95% CI 15.28-20.33; aROR 14.52, 95% CI 12.56-16.78) and cardiac failure (a = 57; ROR 5.55, 95% CI 4.27-7.22; aROR 5.10, 95% CI 3.92-6.64). In the exploratory adjusted analysis, 79 of 80 signals remained significant; only cataract did not (aROR 1.54, 95% CI 0.96-2.48; p = 0.076). CONCLUSION: Mavacamten was associated with expected cardiac safety signals and additional exploratory signals, supporting continued surveillance and careful cardiac monitoring. These hypothesis-generating findings require confirmation in independent data sources.