SEQUOIA-HCM
Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM
Patient / Population Intervention / Exposure Comparison Outcome
In 282 patients with symptomatic obstructive HCM, aficamten improved peak oxygen uptake on exercise testing compared with placebo.
N
282
Design
Double-blind placebo-controlled RCT, phase 3
Endpoint
Change in peak oxygen uptake (pVO2) at 24 weeks
Relevance
3
ResultAficamten increased pVO2 by a least-squares mean difference of 1.74 mL/kg/min (95% CI 1.04-2.44; P<0.001) vs placebo, with improvements in all 10 secondary endpoints.
Maron MS, et al. N Engl J Med. 2024;390(20):1849-1861. 10.1056/NEJMoa2401424
Discussion & critique
Functional surrogate endpoint over 24 weeks rather than hard outcomes. Positioned aficamten as a next-generation cardiac myosin inhibitor with a potentially simpler titration/monitoring profile than mavacamten.