Amgen and Cytokinetics Announce FDA Fast Track Designation for Omecamtiv Mecarbil in Chronic Heart Failure with Reduced Ejection Fraction

May 09, 2020 News /Bio ValleyBIOON/ -- Amgen and its partner Cytokinetics jointly announced recently that the U.S. Food and Drug Administration (FDA) has been granted Fast Track Designation (FTD) for omecamtiv mecarbil, a novel selective cardiac myosin activator currently under development for the treatment of chronic heart failure with reduced ejection fraction (HFrEF).

Fast Track Designation (FTD) is intended to accelerate drug development and expedite the review of drugs for serious conditions, addressing unmet medical needs in critical areas. Investigational drugs granted Fast Track designation allow pharmaceutical companies to engage withFDAEngage in more frequent interactions; if the relevant criteria are met after submission of the marketing application, it will be eligible for accelerated approval and priority review, as well as rolling review.

David M. Reese, M.D., Executive Vice President of Research and Development at Amgen, stated: “FDAThe granting of Fast Track designation marks a significant milestone in the clinical development of omecamtiv mecarbil. Currently, half of patients with heart failure will die within five years of diagnosis, underscoring the urgent need for innovative therapies to treat this serious condition.”

Robert I. Blum, President and Chief Executive Officer of Cytokinetics, stated, “We are pleasedFDAFast Track designation has been granted for omecamtiv mecarbil in the treatment of heart failure. With an aging population, the incidence of heart failure is rising. Currently, we are conducting the GALACTIC-HF study to evaluate the clinical efficacy of this novel myosin activator in high-risk patients.”

GALACTIC-HF is one of the largest global Phase III cardiovascular outcomes trials conducted to date in the field of heart failure treatment. It has completed enrollment of more than 8,200 patients across 35 countries. These patients were either hospitalized for heart failure at the time of study enrollment or had been hospitalized or visited the emergency department for heart failure within one year prior to screening. The study aims to evaluate whether adding omecamtiv mecarbil to standard care reduces 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).

In February this year, Amgen and Cytokinetics announced that the Data Monitoring Committee (DMC) had recently completed the second and final planned interim analysis of the GALACTIC-HF trial, which included consideration of pre-specified criteria for futility and superiority. The DMC reviewed data from the GALACTIC-HF trial and recommended continuing the trial without modifications. Top-line results are expected in the fourth quarter of 2020.

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 the 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 among those diagnosed, approximately half 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 directly converts chemical energy into the mechanical force responsible for 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:FDA Grants Fast Track Designation For Omecamtiv Mecarbil In Heart Failure