Positive results in phase 3 trial with cardiac myosin inhibitor in obstructive HCM


In the phase 3 SEQUOIA-HCM trial, treatment with aficamten improved exercise capacity in patients with obstructive HCM compared with placebo.

Positive results of phase 3 SEQUOIA-HCM trial, in which the effect of the cardiac myosin inhibitor aficamten was evaluated, have been announced. Aficamten significantly improved peak oxygen uptake (pVO2) in patients with obstructive HCM compared with placebo (least square mean difference: 1.74 mL/kg/min; 95%CI: 1.04-2.44; P=0.000002). This improvement was seen across all prespecified subgroups.

Treatment with aficamten also improved all 10 prespecified secondary endpoints, which included KCCQ-CSS at week 12 and 24, the proportion of patients with ≥1 class improvement in NYHA functional class at week 12 and 24, change in provoked LVOT gradient (LVOT-G) at week 12 and 24, proportion with LVOT-G <30 mmHg at week 12 and 24, exercise workload, and guideline-eligibility for septal reduction therapy.

SEQUOIA-HCM was a multicenter, randomized, placebo-controlled, double-blind trial in which 282 patients with symptomatic obstructive HCM were randomized to aficamten or placebo for 24 weeks.  Key inclusion criteria were resting LVOT-G ≥50 mmHg, post-Valsalva LVOT-G ≥50 mmHg, LVEF ≥60% and NYHA class II or III at screening. The primary endpoint was change in pVO2 as measured with cardiopulmonary exercise testing from baseline to week 24.

Aficamten was well-tolerated among patients. Treatment-emergent serious adverse events occurred in 5.6% of patients in the aficamten group compared with 9.3% of patients in the placebo group. LVEF <50% was observed in 3.5% of patients in the aficamten group compared with 0.7% in the placebo group. There were no reports of worsening HF or treatment interruptions due to low LVEF.

Full results from the SEQUOIA-HCM trial will be presented at a medical meeting in 2024.

Source: Press release Cytokinetics December 27, 2023

Study design of the SEQUOIA-HCM trial has been published in JACC Heart Fail.

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