New Treatment in Pipeline for Patients with Hypertrophic Cardiomyopathy

May 14, 2024

Lahey Hospital & Medical Center Investigator Leads Phase 3 Trial Demonstrating Novel Therapy Enhances Exercise Capacity, Improves Symptoms in Patients Obstructive HCM

Burlington, MA - One of the most common genetic heart diseases worldwide, hypertrophic cardiomyopathy (HCM) causes the walls of the left ventricle to become thick and stiff. In about 70 percent of cases, patients with HCM experience obstruction to blood flow, which increases pressures in the heart and can lead to chest pain, shortness of breath and reduced exercise capacity. While invasive interventions can restore selected patients’ quality of life, pharmacologic therapies that are safe, well-tolerated and that reliably improve how patients feel and function remain an unmet need for patients with obstructive HCM.

Now, a phase 3 trial has shown that a cardiac myosin inhibitor called aficamten enhances exercise capacity in patients with HCM and leads to significant relief in the burden of limiting symptoms, improving the quality of patients' lives. The late breaking research was presented by principal investigator Martin S. Maron, MD, director of the Hypertrophic Cardiomyopathy Center at Lahey Hospital & Medical Center (LHMC), today at Heart Failure 2024, a scientific Congress of the European Society of Cardiology. The findings also appear in the New England Journal of Medicine.

“The trial demonstrated that aficamten can reliably and safely lower obstruction to blood flow out of the heart in patients with obstructive HCM using a simple and stepwise dosing regimen and was associated with substantial improvements in clinically relevant endpoints such as exercise capacity and symptoms,” said Maron. “These patients are often on a multitude of medications, and aficamten was effective as combination therapy, but also as monotherapy.”

The phase 3 clinical trial, SEQUOIA-HCM, included 282 patients with symptomatic obstructive HCM from 101 sites in 14 countries in North America, Asia and Europe, making it the largestever obstructive HCM trial. All participants were receiving background medical therapy and had reduced exercise capacity. Patients were randomized 1:1 to aficamten or placebo on top of their background medical therapy.

Over the 24-week treatment period, aficamten improved exercise capacity and was also associated with significant improvements in all secondary end points. Efficacy was evident by week 12, with significant improvements in outflow gradients, health status, and symptoms. The incidence of adverse events was similar between patients treated with aficamten compared with placebo.

“It was impressive to see that the beneficial effects of aficamten occurred rapidly and consistently over the treatment period and that the doses could be adjusted effectively and safely using only site read echocardiography measures," said Maron. “It was also reassuring to see that in the very small number of patients found to have an ejection fraction below 50 percent on aficamten, there was no associated heart failure of the need for dose interruption, and that the effect on ejection fraction was reversible with treatment discontinuation.”

Cytokinetics Inc. provided the funding for this study.

Martin S. Maron has received Consultant/Advisor fees from Imbria, Edgewise, Biomarin and Steering Committee fees for SEQUOIA-HCM from Cytokinetics, Incorporated. For a complete list of additional authors and their disclosures, please see the full article in the New England Journal of Medicine.

About Lahey Hospital & Medical Center

Lahey Hospital & Medical Center (LHMC) is a world-renowned tertiary academic medical center known for its innovative technology, pioneering medical treatments and leading-edge research. As a physician-led hospital, LHMC offers a legacy of care and education committed to putting the patient at the center through a multidisciplinary, collaborative and team-based approach. LHMC’s research efforts and clinical trials cross numerous medical disciplines, providing patients with access to the latest options in treatment and care.

LHMC is a part of Beth Israel Lahey Health, a health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,700 physicians and 39,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

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