Cytokinetics announced that the U.S. Food and Drug Administration (FDA) has accepted and filed its New Drug Application (NDA) for omecamtiv mecarbil, an investigational, selective, small molecule cardiac myosin activator, for the treatment of heart failure with reduced ejection fraction (HFrEF). The FDA assigned the NDA a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2022. The FDA also indicated that it is currently not planning to hold an advisory committee meeting to discuss the application.
Clinical Significance
Robert I. Blum, Cytokinetics’ President and Chief Executive Officer, stated, "More than two million people in the U.S. with HFrEF have signs and symptoms of worsening heart failure despite standard of care therapy, pointing to a clear unmet medical need for more treatment options. We look forward to engaging with the FDA to bring this potential new medicine to patients later this year."
The NDA is supported by results from the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) trial, a Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil. The trial enrolled over 8,000 patients across 945 sites in 35 countries.
Efficacy Data from GALACTIC-HF
GALACTIC-HF demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce the risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care. Additional analyses from GALACTIC-HF demonstrated a greater treatment effect of omecamtiv mecarbil in patients with lower left ventricular ejection fraction (LVEF), as well as other characteristics that may indicate worsening heart failure.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.
The development program for omecamtiv mecarbil is assessing its potential for the treatment of HFrEF. No reduction in the secondary endpoint of time to CV death was observed. Adverse events and treatment discontinuation of study drug were balanced between treatment arms. METEORIC-HF, a second Phase 3 clinical trial of omecamtiv mecarbil is designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity. Results from METEORIC-HF are expected in early 2022.
