Abstract 12690: Mavacamten Treatment in Patients With Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Pooled Safety Analysis of 5 Clinical Trials

Abstract

Introduction: Mavacamten, a cardiac myosin inhibitor, is approved by the US FDA for the treatment of adults with symptomatic obstructive HCM. We present results from an integrated analysis of pooled mavacamten safety data from clinical studies in patients (pts) with obstructive and nonobstructive HCM. Methods: Pts who received ≥1 dose of mavacamten in phase 2 and 3 studies (PIONEER-HCM [end of study date: Jan 12, 2018]; MAVERICK-HCM [Jan 7, 2020]; EXPLORER-HCM [Jul 1, 2020]) and ongoing extension studies (PIONEER-OLE and MAVA-LTE [data cut-off date: Aug 31, 2021]) comprised the pooled analysis population. Results: Data were pooled from a total of 314 unique pts with obstructive (n=260) or nonobstructive (n=54) HCM. Baseline characteristics are shown in the Table. Cumulative time on study (parent + extension) was ≥6 mo for 91% of pts. The mean cumulative duration of mavacamten exposure was 20.2 mo (range: 0.3, 42.5; median: 20.7 mo); 5.4% of pts permanently discontinued treatment due to treatment-emergent adverse events (TEAEs). Total cumulative exposure was 527.6 pt-yrs, and the median average daily dose of mavacamten was 5.7 mg. Generally similar proportions of pts on mavacamten vs placebo experienced grade ≥3, serious, or drug-related TEAEs; few pts experienced TEAEs that led to study discontinuation or drug interruption ( Table ). The exposure-adjusted incidence of adjudicated events in EXPLORER-HCM and MAVA-LTE of heart failure and new-onset atrial fibrillation were 1.42 and 3.07 per 100 pt-yrs, respectively. As previously reported, 4 deaths occurred across studies: 3 in the mavacamten arm due to TEAEs (bacterial endocarditis, cardiac arrest, and acute myocardial infarction [all, n=1]), with none considered related to study drug, and 1 in the placebo arm (sudden death). Conclusion: Integrated evaluation of existing trial data in HCM show that mavacamten is safe and generally well tolerated, irrespective of the presence of obstruction and across multiple doses.