Omecamtiv mecarbil – cardiac myosin activator

Omecamtiv mecarbil – cardiac myosin activator

Omecamtiv mecarbil is a cardiac myosin activator being evaluated in the treatment of heart failure. Two studies published in Lancet have evaluated omecamtiv mecarbil. One was a trial in 34 healthy volunteers [1] while another involved 45 heart failure patients [2] already on optimal medical treatment for heart failure. The first in man study concluded that there is a dose dependent augmentation of left ventricular function with omecamtiv mecarbil. Improvement in stroke volume was to the tune of 15 ml and ejection fraction of seven percent. The dose limiting toxic effect was myocardial ischemia due to excessive prolongation of systolic ejection time. The phase 2 trial showed improvement in cardiac function in those with heart failure due to left ventricular dysfunction and the authors suggested that omecamtiv mecarbil could be the first drug in a new class of therapeutic agents for heart failure.

The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) is an international, multicenter, randomized, double-blind, placebo-controlled, event-driven cardiovascular outcomes trial planning to enroll eight thousand patients [3]. Chronic symptomatic heart failure (New York Heart Association functional class II to IV) with left ventricular ejection fraction of 35% or lower will be enrolled, if they have elevated natriuretic peptides and if currently being in hospital for heart failure or history admission or emergency department visit for heart failure within the past year. Primary efficacy outcome would be time to cardiovascular death or first heart failure event.

References

1. John R Teerlink, Cyril P Clarke, Khalil G Saikali, Jacqueline H Lee, Michael M Chen, Rafael D Escandon, Lyndsey Elliott, Rachel Bee, Mohammad Reza Habibzadeh, Jonathan H Goldman, Nelson B Schiller, Fady I Malik, Andrew A Wolff. Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study. Lancet. 2011 Aug 20;378(9792):667-75.
2. John G F Cleland, John R Teerlink, Roxy Senior, Evgeny M Nifontov, John J V Mc Murray, Chim C Lang, Vitaly A Tsyrlin, Barry H Greenberg, Jamil Mayet, Darrel P Francis, Tamaz Shaburishvili, Mark Monaghan, Mitchell Saltzberg, Ludwig Neyses, Scott M Wasserman, Jacqueline H Lee, Khalil G Saikali, Cyril P Clarke, Jonathan H Goldman, Andrew A Wolff, Fady I Malik. The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet. 2011 Aug 20;378(9792):676-83.
3. John R Teerlink, Rafael Diaz, G Michael Felker, John J V McMurray, Marco Metra, Scott D Solomon, Jason C Legg, Gustavo Büchele, Claire Varin, Christopher E Kurtz, Fady I Malik, Narimon Honarpour. Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF. JACC Heart Fail. 2020 Apr;8(4):329-340.