Cytokinetics Reveals SEQUOIA-HCM Results at ESC Heart Failure 2024

Cytokinetics, Inc. recently announced the primary results from the SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a pivotal Phase 3 clinical trial of aficamten, a treatment for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Dr. Martin Maron, the Principal Investigator, presented these findings at the Heart Failure 2024 congress organized by the European Society of Cardiology. Simultaneously, the results were published in the New England Journal of Medicine.

The SEQUOIA-HCM trial included 282 patients with obstructive HCM. The baseline characteristics between the treatment groups were well-matched, showing consistent symptomatic patients with high resting and post-Valsalva gradients. The study allowed background therapies such as beta-blockers, calcium channel blockers, and disopyramide.

Over a 24-week period, aficamten significantly improved exercise capacity compared to a placebo. This was measured by peak oxygen uptake (pVO2) using cardiopulmonary exercise testing (CPET). Patients treated with aficamten showed an increase of 1.8 ml/kg/min in pVO2, compared to no change in the placebo group. The least square mean (LSM) difference was 1.74 mL/kg/min, with a p-value of 0.000002, indicating strong statistical significance.

The consistency of aficamten's effectiveness was evident across all prespecified subgroups, including variations in age, sex, and baseline characteristics, regardless of beta-blocker therapy use. All ten prespecified secondary endpoints showed statistically significant improvements. Patients experienced functional and symptomatic benefits within two weeks of starting treatment, which were maintained throughout the 24-week period. Aficamten greatly improved post-Valsalva left ventricular outflow tract gradient (LVOT-G) and reduced symptom burden compared to placebo. Significant improvements were noted in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and the New York Heart Association (NYHA) Functional Class.

Moreover, aficamten treatment reduced the need for septal reduction therapy (SRT). Patients initially eligible for SRT spent significantly fewer days eligible for the therapy after 24 weeks of aficamten treatment compared to placebo. Additionally, the treatment resulted in an 80% reduction in NT-proBNP, a cardiac wall stress biomarker, relative to placebo.

A prespecified exploratory responder analysis indicated that aficamten improved both exercise capacity and symptoms. Of the aficamten-treated patients, 42% met the composite responder endpoint compared to 14% in the placebo group, a placebo-corrected difference of 28.7%.

According to Fady I. Malik, M.D., Ph.D., Executive Vice President of Research & Development at Cytokinetics, the SEQUOIA-HCM results demonstrate rapid and sustained improvements in exercise capacity, symptoms, and cardiac function, with no treatment interruptions due to low left ventricular ejection fraction (LVEF). These results support potential regulatory approval for aficamten in both the U.S. and Europe.

Dr. Martin Maron highlighted the remarkable and consistent effects of aficamten across various patient subgroups, including those on beta-blockers, which could transform the treatment landscape for obstructive HCM.

Aficamten was well-tolerated, with fewer treatment-emergent serious adverse events compared to placebo. Only a small number of patients experienced LVEF drops below 50%, with no interruptions in treatment due to low LVEF.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!