SEQUOIA-HCM: Aficamten safe and efficacious for HCM across the globe

Aficamten improved exercise capacity, symptoms, and cardiac biomarkers in patients with obstructive hypertrophic cardiomyopathy (HCM), irrespective of geographical region. The global perspective of the SEQUOIA-HCM trial may provide insights into regional variation regarding therapeutic safety and efficacy.

The phase 3 SEQUOIA-HCM study randomised 282 patients with obstructive HCM 1:1 to aficamten, a next-in-class cardiac myosin inhibitor, plus standard-of-care or to placebo plus standard-of-care. The primary analysis displayed positive trial results [1,2]. Dr Caroline Coats (University of Glasgow, UK) assessed the safety and efficacy of aficamten by geographical region [3]. Participants were categorised into a US cohort (n=94), a Europe/Israel cohort (n=142), and a China cohort (n=46).

There were some differences regarding baseline characteristics between the cohorts, such as the occurrence of atrial fibrillation, the use of disopyramide, NYHA functional class, and resting left ventricular outflow tract (LVOT) gradient. Nevertheless, the 3 cohorts demonstrated similar outcomes for the primary endpoint: the change from baseline to week 24 in peak VO₂ by cardiopulmonary exercise testing (+1.8, +1.4, and +1.8 mL/kg/min; P_interaction=0.88). Secondary efficacy endpoints, such as Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) or improvements in LVOT gradient, did not reveal differences between geographical regions either. Dr Coats mentioned that the incidence of serious adverse events was low and comparable between the tested regions. Lastly, the distribution of doses achieved after titration was also similar.

In summary, aficamten improved several disease parameters in patients with obstructive HCM, regardless of geographical area. The safety profile of aficamten did not differ across these regions.

1. Coats CJ, et al. JACC Heart Fail. 2024;12:199-215.
2. Maron MS, et al. N Engl J Med 2024;390:1849-1861.
3. Coats CJ, et al. Effect of aficamten treatment on patients with hypertrophic obstructive cardiomyopathy by geographical region: results from the SEQUOIA-HCM trial. Hottest trials and trial updates (2), Heart Failure 2025, 17–20 May, Belgrade, Serbia.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 21 May 202517 July 2025