In patients with heart failure with reduced ejection fraction (HFrEF), omecamtiv mecarbil significantly reduced the risk of the primary composite outcome of first HF event of cardiovascular (CV) death, according to data presented at a late-breaking science news briefing from the American Heart Association Scientific Sessions 2020.
“Selectively targeting the cardiac sarcomere with omecamtiv mecarbil, the first-in-class myotrope, is a novel approach to improving cardiac function,” said John R. Teerlink, MD, of San Francisco VAMC/UCSF, who presented the results.
“The central defect in initiating factor in HFrEF is a decrease in systolic function,” Dr. Teerlink explained. “Yet, despite extensive investigative efforts for over a century no therapies for chronic HFrEF that targets this systolic dysfunction have improved patient outcomes and, in fact, most have actually increased mortality.”
Omecamtiv mecarbil is a is an investigational medication that was granted fast track designation by the FDA in May 2020. The drug binds to cardiac myosin, the protein in the heart that transforms chemical energy into mechanical work.
The GALACTIC-HF trial randomly assigned 8,256 patients with symptomatic chronic HF with ejection fraction less than or equal to 35% to omecamtiv mecarbil plus standard HF therapy or placebo plus standard HF therapy. The median follow-up was 22 months.
“Participants in GALACTIC-HF represent one of the broadest ranges of HFrEF patients enrolled in contemporary HF trials,” Dr. Teerlink said.
The average age of patients was 66 years and the population was predominantly male and white.
There was a significant 8% reduction in the risk for composite outcome of time to first HF event or CV death in patients assigned to omecamtiv mecarbil compared with placebo (HR=0.92; 95% CI, 0.86-0.99; P=.0025).
The risk of a first HF event — a component of the primary outcome — was reduced by 7%, but did not reach statistical significance (HR=0.93; 95% CI, 0.86-1.00; P=.06). The risk for cardiovascular death alone was not significantly improved by omecamtiv mecarbil.
To evaluate the potential impact of omecamtiv mecarbil on patient symptoms, the change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score from baseline to week 24 was assessed. An overall joint test statistic P value of 0.028 did not meet the hierarchal multiplicity controlled threshold of 0.002. This secondary endpoint was not met.
Subgroup analyses of the primary composite outcome demonstrated a consistent beneficial effect of omecamtiv mecarbil. However one subgroup – those with baseline LVEF 28% or less – demonstrated significant heterogeneity in treatment effect with a P value of 0.003 and a nominal 16% reduction in the primary endpoint
Omecamtiv mecarbil had no significant effect on blood pressure, renal function, or potassium homeostasis. There was no imbalance between the study arm in adverse events, serious adverse events of adverse events of special interest, including myocardial ischemia and ventricular arrhythmias.
