SEQUOIA-HCM: launch of an international multicenter study to investigate a potential new therapy for hypertrophic cardiomyopathy

The SEQUOIA-HCM study, taking place in 105 centers around the world, is evaluating the effects of aficamten on the management of hypertrophic cardiomyopathy (HCM), a genetic disease that causes thickening of the heart muscle, also known as “left ventricular hypertrophy”.

At the end of 2022, IHU ICAN received a visit from Cytokinetics, an American biopharmaceutical company specializing in muscle activators and inhibitors, and promoter of the SEQUOIA-HCM study conducted within our ICAN Clinical Investigation platform.

The principal investigator at the Pitié-Salpêtrière Hospital, Pr Philippe Charron, collaborated with Cytokinetics to conduct this study, with the support of the ICAN IHU research studies.

The Phase III study is currently being launched, and the first enrolments at the Pitié-Salpêtrière hospital are scheduled for the first quarter of 2023!

What is hypertrophic cardiomyopathy?

Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick, causing the left ventricular muscle to stiffen and lose its ability to relax and allow blood to fill.

This relatively rare disease limits the heart’s pumping function, leading to symptoms such as syncope or loss of consciousness, chest pain, shortness of breath or heart failure.

These symptoms appear mainly during exertion, particularly in patients with obstructive” form of the disease (CMHo). In some cases, the disease is complicated by atrial arrhythmia (with a risk of stroke) or ventricular arrhythmia (with a risk of sudden death).

At present, there is no medical treatment that directly addresses the mechanism responsible for hypertrophic cardiomyopathy (HCM), i.e. the hypercontractility caused by the mutations.

Aficamten: an experimental drug to treat HCM

Designed to reduce the hypercontractility underlying the pathophysiology of HCM, a cardiac myosin inhibitor called aficamten is being developed as a potential chronic oral therapy for HCM patients.

SEQUOIA-HCM: an international multicenter study

Led by Cytokinetics, SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) is an international, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of aficamten in adult patients with symptomatic obstructive hypertrophic cardiomyopathy.

The Phase III study will evaluate the effects of aficamten treatment over a 24-week period on cardiopulmonary exercise capacity and health status in patients with symptomatic CMHo. Some participants in this study will receive a placebo.

The primary objective of this Phase III study is to evaluate the effects of aficamten :

  • On exercise capacity in symptomatic HCMo patients;
  • Health status in patients with symptomatic CMHo.
    • According to the New York Heart Association (NYHA) functional classification;
      o On the gradient of the post-Valsalva segment of the left ventricular ejection pathway.

Study duration: 8.5 months.

Around 270 patients will be included in the study at some 105 centers worldwide. The first patients to be included at the Pitié-Salpêtrière hospital are scheduled for autumn 2022.

Who are the players involved?