The Food and Drug Administration (FDA) has issued a Complete Response Letter to Cytokinetics regarding the New Drug Application (NDA) for omecamtiv mecarbil for the treatment of heart failure with reduced ejection failure (HFrEF).
Omecamtiv mecarbil is a selective small molecule cardiac myosin activator designed to increase contractility without increasing intracellular calcium in cardiac myocytes or myocardial oxygen consumption. The NDA submission included 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 or had a hospitalization or admission to an emergency room for heart failure within 1 year prior to screening.
Results showed that treatment with omecamtiv mecarbil met the primary composite endpoint demonstrating a statistically significant reduction in cardiovascular (CV) death or heart failure events compared with placebo. A greater treatment effect of omecamtiv mecarbil was observed in patients with lower left ventricular ejection fraction. However, no reduction in the secondary endpoint of time to CV death was observed.
After reviewing the application, which also included data from the phase 2b COSMIC-HF study (ClinicalTrials.gov Identifier: NCT01786512), the FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 8 to 3 that the benefits of omecamtiv mecarbil do not outweigh its potential risks in the treatment of HFrEF.
According to the FDA, the GALACTIC-HF study was “not sufficiently persuasive to establish substantial evidence of effectiveness for reducing the risk of heart failure events and cardiovascular death in adults with chronic heart failure with reduced ejection fraction, in lieu of evidence from at least 2 adequate and well-controlled clinical investigations.” The Agency is requiring an additional study of omecamtiv mecarbil in HFrEF patients, though the Company states it has no plans conduct another clinical trial.
“We are disappointed with this outcome, especially considering the high unmet need for innovative treatments for patients suffering from worsening heart failure,” said Robert I. Blum, Cytokinetics’ President & CEO. “We are humbled by the support of the heart failure community and will engage with FDA and consider what may be next steps for omecamtiv mecarbil in the US.”
Cytokinetics receives Complete Response Letter from FDA for New Drug Application for omecamtiv mecarbil. News release. Cytokinetics. February 28, 2023. Accessed March 2, 2023. https://ir.cytokinetics.com/news-releases/news-release-details/cytokinetics-receives-complete-response-letter-fda-new-drug.