Efficacy of aficamten according to geographic location of patients with hypertrophic obstructive cardiomyopathy

Background/Aims Obstructive HCM (oHCM) affects people across all geographic regions, ethnicities, and socioeconomic groups. In the SEQUOIA-HCM trial (NCT05186818), aficamten, an oral selective cardiac myosin inhibitor, improved exercise capacity, left ventricular outflow gradients (LVOT-G), and symptoms in oHCM. It is unknown if dosing, safety, or treatment response may vary by geographic region. Methods Participants were randomized 1:1 to daily aficamten (5–20 mg) or placebo for 24 weeks. Participants were grouped by geographic region (North America, China, and Europe, including Israel). Baseline characteristics and treatment effects on peak oxygen uptake (pVO2) and secondary endpoints were compared across geographic groups. Results In all, 282 patients were enrolled in 14 countries: 142 (50%) in Europe, including Israel; 94 (33%) in North America; and 46 (16%) in China. Patients had a higher body mass index and older age in Europe (59.7 years) and North America (61.7 years) than in China (51.8 years). More patients were New York Heart Association (NYHA) class II in Europe (81.7%) and China (93.5%) than North America (58.5%). Baseline Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) was higher in China (82.4) than Europe (73.1) or North America (73.2). The benefit of aficamten on pVO2 was not modified by region (interaction p=0.88) and all secondary endpoints improved with aficamten treatment, acknowledging the analysis was underpowered to detect regional differences. The occurrences of serious adverse events and left ventricular ejection fraction <50% were low and similar by region. Conclusion In SEQUOIA-HCM, the dosing, safety, and treatment effects of aficamten were consistent across geographic regions despite differences in baseline characteristics of patients with oHCM.