Cytokinetics Shares SEQUOIA-HCM Data at ESC Congress 2024

Cytokinetics, Incorporated has unveiled new data from its SEQUOIA-HCM Phase 3 clinical trial, which investigates the efficacy of aficamten in patients suffering from symptomatic obstructive hypertrophic cardiomyopathy (HCM). The findings were presented at the European Society of Cardiology Congress 2024 in London, accompanied by four simultaneous publications in leading cardiac journals.

The trial has demonstrated promising outcomes, including beneficial cardiac remodeling, improvements in cardiac structure and function, and symptom relief. These findings have been showcased in three Late Breaking Clinical Trial presentations and one oral presentation, emphasizing the broad spectrum of aficamten's potential benefits.

Stephen Heitner, M.D., Vice President, Head of Clinical Research at Cytokinetics, highlighted the robust evidence supporting aficamten's positive impact on clinical outcomes, symptoms, and cardiac biomarkers. He noted the potential for aficamten to modify the disease by improving heart architecture in patients with obstructive HCM. The data presented is integral to Cytokinetics' ongoing rolling New Drug Application (NDA) submission for aficamten, expected to be finalized in the third quarter of 2024.

Additional insights were provided by Ahmad Masri, M.D., Director of the Hypertrophic Cardiomyopathy Center at Oregon Health & Science University, who presented data from the cardiac magnetic resonance (CMR) sub-study within SEQUOIA-HCM. The sub-study involved 57 patients, 50 of whom completed it. Those treated with aficamten showed significant improvements, including a reduction in left ventricular mass index (LVMI) and favorable cardiac remodeling.

Further analyses were presented by Sheila Hegde, M.D., M.P.H., from Brigham and Women’s Hospital, who discussed the echocardiographic data from SEQUOIA-HCM. Treatment with aficamten led to significant enhancements in cardiac structure and function, such as reductions in left ventricular outflow tract gradients (LVOT-G) and improvements in left ventricular ejection fraction (LVEF). These improvements were linked to better exercise capacity, symptom relief, and quality of life.

John A. Spertus, M.D., M.P.H., from the University of Missouri Kansas City, presented on the impact of aficamten on patient symptom burden. The data indicated that aficamten significantly improved health status, including symptoms, function, and quality of life, as measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS) and the Seattle Angina Questionnaire Summary Score (SAQ-SS).

Caroline Coats, M.D., Ph.D., from the University of Glasgow, presented a pre-specified secondary analysis focusing on cardiac biomarkers NT-proBNP and high sensitivity cardiac troponin (hs-cTnI). The results indicated an 80% reduction in NT-proBNP levels and significant improvements in pVO2 with aficamten treatment, suggesting these biomarkers could serve as useful tools for monitoring treatment response.

Aficamten, a selective small molecule cardiac myosin inhibitor, was designed to mitigate myocardial hypercontractility associated with HCM by reducing active actin-myosin cross bridges during each cardiac cycle. This therapeutic approach has shown potential in improving exercise capacity and relieving symptoms in HCM patients, and its long-term effects on cardiac structure and function are under continuous evaluation.

The development program for aficamten is robust, encompassing various clinical trials such as MAPLE-HCM, ACACIA-HCM, CEDAR-HCM, and FOREST-HCM. These studies aim to further assess aficamten's efficacy across different patient populations, including those with non-obstructive HCM and pediatric patients.

Hypertrophic cardiomyopathy (HCM) is a condition characterized by abnormal thickening of the heart muscle, leading to reduced relaxation and filling of the left ventricle, and consequentially impaired cardiac function. It is the most common monogenic inherited cardiovascular disorder, with significant portions of the affected population remaining undiagnosed. Patients with HCM are at increased risk for severe cardiovascular complications, including atrial fibrillation, stroke, and sudden cardiac death.

Cytokinetics is poised to submit an NDA to the FDA and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) based on the positive SEQUOIA-HCM trial results. The company continues to explore aficamten’s potential to become a leading therapeutic option for HCM patients worldwide.

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