Aficamten Delivers Positive Results in SEQUOIA-HCM

Aficamten, a novel cardiac myosin inhibitor, improves outcomes for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM), according to top-line results from the phase III SEQUOIA-HCM trial released Wednesday by drugmaker Cytokinetics.

When added to standard care, the agent led to a “clinically meaningful” increase in exercise capacity after 24 weeks of treatment, indicated by a significant rise in peak oxygen uptake during cardiopulmonary exercise testing (least square mean difference 1.74 mL/kg/min). Results were consistent across all prespecified subgroups, the company reported.

Moreover, aficamten improved all 10 prespecified secondary endpoints, which included assessments of heart failure symptoms, NYHA functional class, changes in provoked left ventricular outflow tract (LVOT) gradients, exercise workload, and guideline eligibility for septal reduction therapy.

The therapy was well tolerated, with a rate of treatment-emergent serious adverse events of 5.6% in the aficamten arm and 9.3% in the placebo arm. The proportion of patients who developed an LVEF of less than 50% was 3.5% with aficamten and 0.7% with placebo, although there were no cases of worsening heart failure and no treatment interruptions due to low LVEF, Cytokinetics said.

The company aims to make aficamten—which has been designated a breakthrough therapy by the US Food and Drug Administration and the National Medical Products Administration in China—the second cardiac myosin inhibitor on the market. The FDA approved the first, mavacamten (Camzyos; Bristol Myers Squibb), for patients with symptomatic obstructive HCM in April 2022.

SEQUOIA-HCM, with 282 patients who had symptomatic HCM and LVOT obstruction, is the pivotal phase III trial of aficamten. Full results are slated to be presented at an upcoming medical conference in 2024. Previously, in the REDWOOD-HCM Open Label Extension study, the drug was shown to reduce LVOT gradients and relieve heart failure symptoms and improve patient-measured health status.

Aficamten also is being evaluated in two other ongoing phase III trials—MAPLE-HCM in patients with obstructive HCM (compared with metoprolol) and ACACIA-HCM in patients with symptomatic nonobstructive HCM.