Cytokinetics Launches Phase 3 COMET-HF Trial for Omecamtiv Mecarbil in Severe Heart Failure

SOUTH SAN FRANCISCO, Calif., Dec. 03, 2024 – Cytokinetics, Incorporated has revealed the start of COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a Phase 3 clinical trial that investigates the efficacy of omecamtiv mecarbil in patients suffering from symptomatic heart failure (HF) with a severely reduced ejection fraction. Omecamtiv mecarbil is a pioneering selective cardiac myosin activator being developed to treat heart failure with a severely reduced ejection fraction. This trial, conducted in collaboration with the Duke Clinical Research Institute (DCRI), aims to address the needs of patients with limited treatment options who remain at high risk despite following guideline-directed medical therapy.

Dr. Stuart Kupfer, Senior Vice President and Chief Medical Officer, expressed satisfaction with the initiation of COMET-HF, aiming to evaluate the drug's potential benefits. COMET-HF's design is influenced by positive data from previous trials like GALACTIC-HF and comprehensive consultations with the FDA and the heart failure community. The trial incorporates pragmatic features to improve study efficiency and reduce patient burden. The goal is to generate additional evidence of omecamtiv mecarbil’s potential therapeutic benefits for patients with significant unmet needs.

Dr. Michael Felker of DCRI emphasized the urgent need for new treatments for severe heart failure. Despite advancements in heart failure treatments, patients still face high risks of hospitalization and death. Through the collaboration with Cytokinetics, DCRI aims to leverage its extensive experience in cardiovascular clinical trials to advance innovation for patient care.

COMET-HF is a large-scale, multinational, randomized, placebo-controlled trial designed to assess the efficacy and safety of omecamtiv mecarbil in patients with symptomatic heart failure and severely reduced ejection fraction. The primary endpoint of the trial is the time to the first event in a composite endpoint encompassing cardiovascular death, first heart failure event, left ventricular assist device (LVAD) implantation or cardiac transplantation, and stroke. Secondary endpoints will evaluate the risks of individual components, such as heart failure hospitalization, cardiovascular death, stroke, and irreversible morbidity/mortality based on the composite endpoint.

Approximately 1,800 patients will be randomized in a 1:1 ratio to receive either omecamtiv mecarbil or a placebo. To qualify for the trial, patients must have symptomatic heart failure with a left ventricular ejection fraction below 30%, an NT-proBNP level of at least 1,000 pg/mL, and a heart failure event within the previous six months. Eligible participants will first undergo a two-week run-in period, during which those intolerant to the drug or with inappropriate plasma concentrations will be excluded. Following this period, a two-week washout phase will occur before randomization. Patients will receive omecamtiv mecarbil, up to 50 mg twice daily based on plasma concentration, or a placebo, continuing until at least 850 primary composite endpoint events are recorded.

Omecamtiv mecarbil is an innovative cardiac myosin activator that enhances heart contractility by targeting contractile mechanisms directly, without increasing intracellular calcium levels or myocardial oxygen consumption. Previous research, including the GALACTIC-HF trial, has demonstrated that omecamtiv mecarbil can reduce the risk of cardiovascular death or heart failure events compared to a placebo in patients receiving standard care. The safety profile showed no significant difference in adverse events or treatment discontinuation between the omecamtiv mecarbil and placebo groups.

Cytokinetics is a biopharmaceutical company focused on developing drugs for diseases that compromise cardiac muscle performance, leveraging its expertise in muscle biology and muscle function mechanics. The company's late-stage development programs include further trials and regulatory submissions for aficamten and other promising drug candidates aimed at treating heart failure and hypertrophic cardiomyopathy.

The Duke Clinical Research Institute, a part of the Duke University School of Medicine, is acclaimed for its extensive experience in conducting large-scale clinical research to improve global health through innovative studies.