Heart failure continues to be a major global health problem with a pronounced 
impact on morbidity and mortality and very limited drug treatment options 
especially with regard to inotropic therapy. Omecamtiv mecarbil is a 
first-in-class cardiac myosin activator, which increases the proportion of 
myosin heads that are tightly bound to actin and creates a force-producing state 
that is not associated with cytosolic calcium accumulation. Phase I and phase II 
studies have shown that it is safe and well tolerated. It produces 
dose-dependent increases in systolic ejection time (SET), stroke volume (SV), 
left ventricular ejection fraction (LVEF), and fractional shortening. In the 
ATOMIC-AHF trial, intravenous (IV) omecamtiv mecarbil did not improve dyspnoea 
overall but may have improved it in a high-dose group of acute heart failure 
patients. It did, however, increase SET, decrease left ventricular end-systolic 
diameter, and was well tolerated. The COSMIC-HF trial showed that a 
pharmacokinetic-based dose-titration strategy of oral omecamtiv mecarbil 
improved cardiac function and reduced ventricular diameters compared to placebo 
and had a similar safety profile. It also significantly reduced plasma 
N-terminal-pro B-type natriuretic peptide compared with placebo. The GALACTIC-HF 
trial is now underway and will compare omecamtiv mecarbil with placebo when 
added to current heart failure standard treatment in patients with chronic heart 
failure and reduced LVEF. It is expected to be completed in January 2021. The 
ongoing range of preclinical and clinical research on omecamtiv mecarbil will 
further elucidate its full range of pharmacological effects and its clinical 
usefulness in heart failure.