Cytokinetics has announced positive topline results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial of Aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The study demonstrated that treatment with Aficamten significantly improved exercise capacity compared to placebo, with a notable increase in peak oxygen uptake (pVO2) by a least square mean difference of 1.74 mL/kg/min (p=0.000002). The treatment effect was consistent across all prespecified subgroups, including patients both receiving and not receiving background beta-blocker therapy. Furthermore, statistically significant and clinically meaningful improvements were observed in all 10 prespecified secondary endpoints, such as the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and changes in the New York Heart Association (NYHA) functional class.
Aficamten was well-tolerated, showing an adverse event profile comparable to placebo, with treatment emergent serious adverse events occurring in 5.6% of Aficamten patients versus 9.3% on placebo. Notably, the study observed low rates of left ventricular ejection fraction (LVEF) below 50%, with only 3.5% of Aficamten patients affected compared to 0.7% on placebo, and no instances of worsening heart failure or treatment interruptions due to low LVEF. These results align with previous findings from the Phase 2 REDWOOD-HCM trial and the ongoing FOREST-HCM open label extension trial, suggesting that Aficamten could become the cardiac myosin inhibitor of choice for obstructive HCM. Full results will be presented at a medical conference in 2024.
