Abstract 4134320: Integrated safety and tolerability of mavacamten treatment over 5 years in patients with obstructive hypertrophic cardiomyopathy

Background: Mavacamten, a cardiac myosin inhibitor, is approved across 5 continents for the treatment of obstructive hypertrophic cardiomyopathy (HCM). Long-term data of mavacamten are available from multiple studies, providing the opportunity to further understand mavacamten long term safety, including adverse events (AEs) of clinical interest. Aim: To present integrated safety data of patients who received mavacamten treatment for obstructive HCM across 5 studies. Methods: The pooled population included all patients who received ≥1 dose of mavacamten in PIONEER-HCM, PIONEER-Open Label Extension (data cut-off: May 31, 2022), EXPLORER-HCM, MAVA-Long-Term Extension (EXPLORER cohort; data cut-off: August 31, 2023) and VALOR-HCM including long-term extension (data cut-off: November 11, 2022). Results: The population consisted of 368 patients (mean [SD] age: 59.4 [12.2] years; male: 57.1%; White: 90.8%), including 350 patients who continued onto an extension study after completing a parent study. The majority of patients (57.6%) had a cumulative time on study of ≥3 years. Forty (10.9%) patients permanently discontinued treatment (13 due to AEs). In total, 20.7% of patients had a treatment emergent AE (TEAE) of Grade ≥3 and 14.7% had a TEAE leading to drug interruption. Overall, 4.3% of patients had drug-related serious TEAEs and 1.6% had a TEAE leading to death. The cumulative exposure adjusted incidence rates (EAIR) of all TEAEs, including AEs of clinical interest (atrial fibrillation [AF], ejection fraction [EF] decreased and heart failure [HF]), decreased as exposure increased over time, from 347.1/100 patient-years (P-Y) at Week 60 (~year 1) to 271.8/100 P-Y at Week 252 (~year 5). The EAIR of AF decreased over time from 13.3/100 P-Y at Week 60 (~year 1) to 6.2/100 P-Y at Week 252 (~year 5) ( Figure ). The EAIR for EF decreased and HF also decreased over time ( Figure ). Conclusions: This integrated analysis of all patients with obstructive HCM treated with mavacamten across the 5 clinical studies over 5 years demonstrated that mavacamten treatment is generally well tolerated and that the EAIRs of selected TEAEs of clinical interest (AF, EF decreased and HF) decreased as exposure increased over time.