Amgen, Cytokinetics and Servier Announce Completion of Final Interim Analysis in Phase III GALACTIC-HF Trial of Omecamtiv Mecarbil for Chronic Heart Failure

February 28, 2020 News /BioonBIOON/ -- Amgen, in collaboration with its partners Cytokinetics and Servier, recently announced that the Data Monitoring Committee (DMC) has completed the second and final planned interim analysis of the Phase III GALACTIC-HF trial evaluating the novel cardiac myosin activator omecamtiv mecarbil for the treatment of heart failure. This analysis included assessments against pre-specified criteria for futility and superiority. The DMC reviewed data from the GALACTIC-HF trial and recommended continuing the study without modifications. Top-line results are expected in the fourth quarter of 2020.

GALACTIC-HF is one of the largest global Phase III cardiovascular outcomes studies conducted to date in the field of heart failure treatment. Enrollment has been completed across 35 countries, with more than 8,200 patients recruited. These patients were either hospitalized for heart failure at the time of study enrollment or had been hospitalized for heart failure or visited an emergency department for heart failure within one year prior to screening. The study aimed to evaluate whether the addition of omecamtiv mecarbil to standard care could reduce the risk of heart failure events (hospitalization for heart failure and other urgent treatments for heart failure) and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF).

The second interim analysis was conducted after the number of cardiovascular deaths among patients reached a prespecified threshold, as outlined in the GALACTIC-HF trial protocol. If the interim analysis indicated a low probability of demonstrating clinically and statistically significant benefits in the primary endpoint for the omecamtiv mecarbil plus standard care group compared to the placebo plus standard care group, the futility analysis allowed for potential early termination of the trial. Conversely, if both the primary composite endpoint and the secondary endpoint (time to cardiovascular death) achieved statistical significance, the superiority analysis permitted early termination of the trial, with adjusted statistical thresholds for interim review.

Molecular structure of omecamtiv mecarbil (Image source: Wikipedia)

Heart failure is a serious condition affecting more than 26 million people worldwide, approximately half of whom have reduced left ventricular function. It is a leading cause of hospitalization and readmission among individuals aged 65 years and older. Despite the widespread use of standard therapies and advances in care, the prognosis for patients with heart failure remains poor. It is estimated that approximately one in five people aged 40 years and older is at risk of developing heart failure, and about half of those diagnosed with heart failure die within five years of their initial hospitalization.

Omecamtiv mecarbil is a novel, selective cardiac myosin activator that binds to the catalytic domain of myosin. Preclinical studies have demonstrated that cardiac myosin activators can increase myocardial contractility without affecting intracellular calcium concentrations in cardiomyocytes or myocardial oxygen consumption. Cardiac myosin is a cytoskeletal motor protein in cardiomyocytes that is directly responsible for converting chemical energy into the mechanical force that leads to myocardial contraction.

Currently, omecamtiv mecarbil is being developed for the treatment of heart failure with reduced ejection fraction (HFrEF) through a collaboration between Amgen and Cytokinetics, with funding and strategic support from Servier. The team is conducting a comprehensive Phase III clinical development program, which includes two Phase III trials: (1) the GALACTIC-HF trial, evaluating the impact of omecamtiv mecarbil versus placebo on cardiovascular outcomes in patients; and (2) the METEORIC-HF trial, assessing the effect of omecamtiv mecarbil versus placebo on patients' exercise capacity (evaluated using cardiopulmonary exercise testing). (Bioon.com)

Original Source:Amgen, Cytokinetics and Servier Announce Continuation of GALACTIC-HF After Planned Interim Analysis