The Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction (HFrEF).
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator designed to increase contractility without increasing intracellular calcium in cardiac myocytes or myocardial oxygen consumption.
The NDA is supported by data from the phase 3 GALACTIC-HF trial (ClinicalTrials.gov Identifier: NCT02929329), which assessed the efficacy and safety of omecamtiv mecarbil in 8256 adults who were either hospitalized at the time of enrollment for a primary reason of heart failure (HF) or had a hospitalization or admission to an emergency room for HF within 1 year prior to screening. Patients were randomly assigned to receive either oral omecamtiv mecarbil or placebo twice daily plus standard of care. The primary composite endpoint was the time to cardiovascular (CV) death or first HF event through study completion, up to 208 weeks.
Findings showed that the study met the primary composite endpoint, demonstrating a statistically significant effect with omecamtiv mecarbil in reducing CV death or HF events compared with placebo (hazard ratio 0.92 [95% CI, 0.86-0.99]; P =.0252). However, no reduction in the secondary endpoint of time to CV death was observed.
Additional analyses showed a greater treatment effect of omecamtiv mecarbil in patients with lower left ventricular ejection fraction (EF). Treatment with omecamtiv mecarbil demonstrated a 15% (HR 0.85; 95% CI, 0.74-0.97; P =.016) and 17% (HR 0.83; 95% CI, 0.73-0.95; P =.005) relative risk reduction for the primary endpoint (first HF event or CV death) in the lower 2 EF quartiles (EF≤ 22% and EF 23-28%, respectively). A statistically significantly greater reduction in NT-proBNP was also observed among patients with lower ejection fraction.
“This is an exciting milestone and important next step towards the commercial launch of omecamtiv mecarbil,” said Robert I. Blum, Cytokinetics’ President and CEO. “More than 2 million people in the US 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.”
A Prescription Drug User Fee Act (PDUFA) target date of November 30, 2022 has been set for the application.
- Cytokinetics announces FDA acceptance of New Drug Application for omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction. News release. Cytokinetics, Inc. Accessed February 4, 2022. https://www.globenewswire.com/news-release/2022/02/04/2379227/35409/en/Cytokinetics-Announces-FDA-Acceptance-of-New-Drug-Application-for-Omecamtiv-Mecarbil-for-the-Treatment-of-Heart-Failure-With-Reduced-Ejection-Fraction.html
- Cytokinetics announces secondary analysis of GALACTIC-HF presented in late breaking clinical trial session at the American College of Cardiology 70th Annual Scientific Session and published in the Journal of American College of Cardiology. News release. Cytokinetics, Inc. May 17, 2021. Accessed February 4, 2022. https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-announces-secondary-analysis-galactic-hf-presented