Omecamtiv mecarbil improves cardiac function in chronic heart failure trial

Amgen and Cytokinetics Incorporated have announced that data from the expansion phase of COSMIC-HF, a Phase 2 trial evaluating omecamtiv mecarbil in patients with chronic heart failure, showed statistically significant improvements in several measures of cardiac function.

This includes systolic ejection time, stroke volume and N-terminal-pro-brain natriuretic peptide. The pharmacodynamic effects of omecamtiv mecarbil were generally dose dependent. 

Omecamtiv mecarbil is a novel cardiac myosin activator. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. Cardiac myosin activators are thought to accelerate the rate-limiting step of the myosin enzymatic cycle and shift the enzymatic cycle in favour of the force-producing state. Preclinical research has shown that cardiac myosin activators increase contractility in the absence of changes in intracellular calcium in cardiac myocytes.

Omecamtiv mecarbil resulted in statistically significant decreases in cardiac dimensions

The expansion phase of COSMIC-HF was designed to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of oral omecamtiv mecarbil in 448 patients with chronic heart failure and left ventricular systolic dysfunction. Data from the expansion phase showed that pharmacokinetic-based dose titration adequately controlled patient exposure to omecamtiv mecarbil and resulted in statistically significant decreases in cardiac dimensions and heart rate in the dose-titration group.  

Adverse events, including serious adverse events, in patients on omecamtiv mecarbil appeared comparable to those on placebo. A small increase in troponin was seen among subjects receiving omecamtiv mecarbil.

“The positive results from the COSMIC-HF trial of omecamtiv mecarbil are encouraging,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We are committed to working with Cytokinetics to better understand the data and its potential role in the treatment of heart failure patients.”

“We are pleased that this Phase 2 trial of omecamtiv mecarbil met the objectives related to safety, tolerability, pharmacokinetics and pharmacodynamics in a population of chronic heart failure patients,” said Robert I. Blum, president and CEO at Cytokinetics. “Omecamtiv mecarbil has the potential to offer a new treatment option for patients with heart failure; we look forward to working with Amgen and the medical community to better understand the potential clinical application of this novel drug candidate.”