Amgen and its partner Cytokinetics recently announced that the US Food and Drug Administration (FDA) has granted omecamtiv mecarbil fast-track qualification (FTD), which is a new type of selective myocardial myosin activator. Developed to treat chronic heart failure (HFrEF) with reduced ejection fraction.
The Fast Track Qualification (FTD) is designed to accelerate the development and rapid review of drugs for serious diseases to address serious unmet medical needs in key areas. Obtaining fast-track qualifications for research drugs means that pharmaceutical companies can interact with FDA more frequently during the R & D phase. After submitting marketing applications, they are eligible for accelerated approval and priority review if they meet the relevant standards. In addition, they are also eligible for rolling review.
David M. Reese, Executive Vice President of Amgen R & D and MD Highlights the urgent need for innovative therapies to treat this serious disease. "
Robert I. Blum, President and CEO of Cytokinetics, said: "We are very pleased that the FDA has granted omecamtiv mecarbil fast-track qualification for heart failure. As the population ages, the incidence of heart failure is increasing. Currently, we are developing GALACTIC -HF study to evaluate the clinical effect of this new myosin activator in high-risk patients. "
GALACTIC-HF is one of the largest phase III global cardiovascular outcome studies to date in the field of heart failure treatment. It has now enrolled more than 8,200 patients in 35 countries. These patients were due to heart failure when they entered the study Hospitalization, or hospitalization or emergency room due to heart failure within one year before screening. The purpose of the study was to assess whether adding omecamtiv mecarbil to standard care can reduce the risk of heart failure events (heart failure hospitalization and other emergency treatment of heart failure) and cardiovascular death in patients with heart failure (HFrEF) with reduced ejection fraction.
In February of this year, Amgen and Cytokinetics announced that the Data Monitoring Committee (DMC) had recently completed the second and final planned mid-term analysis of the GALACTIC-HF trial, which included consideration of pre-specified criteria for invalidity and superiority. DMC reviewed the data from the GALACTIC-HF trial and recommended that the trial be continued without change. Top-line results are expected to be obtained in the fourth quarter of 2020.
The second interim analysis was carried out after the cardiovascular death of the patients specified in the GALACTIC-HF trial protocol reached a pre-specified number. If the interim analysis shows that the omecamtiv mecarbil + standard care group has a clinically significant and statistically significant clinical benefit at the primary endpoint compared to the placebo + standard care group, then the ineffectiveness analysis allows potential early discontinuation of the trial . If the primary composite endpoint and the secondary endpoint (cardiovascular death time) reach statistical significance, the superiority analysis allows early termination of the trial and adjustment of the statistical threshold for the mid-term review.
Molecular structure of omecamtiv mecarbil (Image source: Wikipedia)
Heart failure is a serious disease that affects more than 26 million people worldwide, and about half of them have reduced left ventricular function. The disease is the main cause of hospitalization and readmission for people aged 65 and over. Despite widespread use of standard treatments and advances in care, the prognosis for patients with heart failure is still poor. It is estimated that about one-fifth of people over the age of 40 are at risk of heart failure, and about half of patients diagnosed with heart failure will die within 5 years of their first hospitalization.
Omecamtiv mecarbil is a new, selective, myocardial myosin activator that binds to the catalytic domain of myosin. Preclinical studies have shown that myocardial myosin activator can increase myocardial contractility without affecting the intracellular calcium concentration of myocardial cells or myocardial oxygen consumption. Cardiac myosin is a cytoskeletal motor protein in cardiomyocytes, which is directly responsible for converting chemical energy into mechanical force that causes myocardial contraction.
Currently, omecamtiv mecarbil is developing a treatment for heart failure (HFrEF) with reduced ejection fraction, under the cooperation of Amgen and Cytokinetics, with the support and strategic support of Servier. The team is carrying out a comprehensive phase III clinical development project, which includes two phase III trials: (1) GALACTIC-HF trial to evaluate the impact of omecamtiv mecarbil and placebo on patients' cardiovascular outcomes; (2) METEORIC -HF test to evaluate the effect of omecamtiv mecarbil and placebo on the exercise capacity of patients (using the cardiopulmonary exercise test).