Cytokinetics Shares New SEQUOIA-HCM Data at HCMS Sessions

Cytokinetics, Incorporated, recently showcased new findings from the SEQUOIA-HCM Phase 3 clinical trial on aficamten at the Hypertrophic Cardiomyopathy Medical Society (HCMS) Scientific Sessions. This trial evaluated aficamten's effectiveness in treating patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). The data, presented by Dr. Anjali T. Owens, highlighted significant improvements in various cardiac indices among patients treated with aficamten compared to those on a placebo over a 24-week period.

The key findings from this new analysis include notable improvements in several areas for patients treated with aficamten. Specifically, a significant reduction in maximal wall thickness was observed in 47.9% of aficamten-treated patients compared to 30.7% in the placebo group. Additionally, left atrial volume index (LAVI) improvements were noted in 46.8% of aficamten users versus 18.7% in the placebo group. There was also a notable resolution of ECG changes linked to left ventricular hypertrophy in 19.0% of the aficamten group compared to 4.3% in the placebo group. Furthermore, aficamten helped normalize hyperdynamic left ventricular ejection fraction in 35.2% of patients, as opposed to 20.7% in those on placebo. Lastly, a significant reduction of NT-proBNP levels by 50% or more was observed in 81.7% of aficamten users compared to just 7.1% in the placebo group.

Overall, 83.8% of patients on aficamten exhibited beneficial effects in at least one of these areas, compared to 39.3% of those on placebo. This significant difference underscores aficamten's potential in positively remodeling cardiac structure and function.

Stephen Heitner, M.D., Vice President and Head of Clinical Research at Cytokinetics, expressed optimism about these findings. He emphasized the promising remodeling effects of aficamten on cardiac structure and function, as well as its electrophysiological and biochemical benefits. Cytokinetics plans to further explore the long-term clinical outcomes of aficamten through ongoing studies, including FOREST-HCM, an open-label extension clinical study.

Due to Hurricane Helene's impact on the Atlanta area, the HCMS Scientific Sessions shifted from in-person to virtual presentations. Consequently, Cytokinetics decided to withdraw their poster on the efficacy and safety of aficamten in patients with very high left ventricular outflow tract gradients. The company intends to resubmit this poster for future presentations at in-person medical meetings.

Aficamten, a selective small molecule cardiac myosin inhibitor developed by Cytokinetics, has undergone extensive optimization to ensure a beneficial therapeutic index and pharmacokinetic properties. Designed to reduce myocardial hypercontractility associated with HCM, aficamten binds directly to cardiac myosin, preventing it from entering a force-producing state. This results in reduced myocardial contractility.

The clinical development program for aficamten aims to assess its potential in improving exercise capacity, alleviating symptoms of HCM, and determining its long-term effects on cardiac structure and function. Besides SEQUOIA-HCM, which produced positive results in treating symptomatic obstructive HCM, aficamten is also being evaluated in several other clinical trials. These include MAPLE-HCM, which compares aficamten monotherapy to metoprolol monotherapy, ACACIA-HCM, which focuses on non-obstructive HCM, CEDAR-HCM for pediatric patients with obstructive HCM, and FOREST-HCM, an open-label extension study.

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the heart muscle, leading to reduced heart function and symptoms such as chest pain, dizziness, and shortness of breath. HCM affects approximately 280,000 diagnosed patients, with many more undiagnosed individuals in the U.S. The disease can lead to severe complications, including atrial fibrillation, stroke, and sudden cardiac death, particularly in younger individuals and athletes.

Cytokinetics, a late-stage biopharmaceutical company, is dedicated to developing treatments for debilitating diseases affecting cardiac muscle performance. Their work on aficamten and other drug candidates aims to address the unmet needs in cardiovascular health.