Omecamtiv Mecarbil Shown to Improve Cardiac Function, Clinical Outcomes in GALACTIC-HF

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Findings from the GALACTIC-HF trial presented at AHA Scientific Sessions 2020 showed that patients with heart failure (HF) with reduced ejection fraction who took omecamtiv mecarbil showed a significant 8% relative risk reduction in a composite of a HF event or death from cardiovascular causes, compared with those taking placebo.

A new therapy that directly targets the heart function reduced the risk of hospitalization or emergency department visits in patients with heart failure (HF) with reduced ejection fraction (HFrEF), according to a study released today.

Presented at American Heart Association Scientific Sessions 2020, the randomized, placebo-controlled, phase 3 Global Approach to Lowering Adverse Cardiac Outcomes through Improving Contractility in HF (GALACTIC-HF) trial sought to assess whether omecamtiv mecarbil, from Amgen, would lower the risk of HF events and cardiovascular death in patients with HFrEF.

Findings from the GALACTIC-HF trial were simultaneously published in the New England Journal of Medicine.

HFrEF is characterized by the decrease in systolic function and cardiac output, and to date, no medication works directly to boost systolic function and improve outcomes. In fact, many therapies studied even increased the risk of mortality.

However, a new class of therapies, called cardiac myosin activators, have shown promise in improving myocardial function by directly augmenting cardiac contractility. The first in the class, omecamtiv mecarbil, when given in short-term intravenous administration, was shown to improve cardiac performance in early clinical studies.

Moreover, patients with HFrEF administered omecamtiv mecarbil for 20 weeks were shown to exhibit increases in left ventricular systolic ejection time and stroke volume, decreases in left ventricular systolic and diastolic volumes (indicating beneficial reverse cardiac remodeling), and reduced plasma natriuretic peptide levels and heart rate.

Collecting a patient cohort of inpatients and outpatients (n = 8256) with symptomatic chronic HF and an ejection fraction ≤ 35%, researchers randomized (1:1 ratio) participants to receive omecamtiv mecarbil (25 mg, 37.5 mg, or 50 mg twice daily) (n = 4120; 77.6% White; 78.8% male) or placebo (n = 4112; 77.8% White; 78.7% male), in addition to standard HF therapy.


The study examined the primary outcome of a composite of a HF event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death, whichever occurred first, in a time-to-event analysis, with secondary outcomes assessing:

  • cardiovascular death
  • change in total symptom score on the Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to week 24
  • first HF hospitalization
  • death from any cause

After a median of 21.8 months, a primary outcome event occurred in 1523 of 4120 patients (37%) administered omecamtiv mecarbil and in 1607 of 4112 patients (37%) in the placebo group, indicating a signficant 8% risk reduction in incidence of a composite of a HF event or death from cardiovascular causes (hazard ratio (HR) = 0.92; 95% CI, 0.86–0.99; P = .03).

In assessing secondary outcomes, a similar 808 patients (19.6%) from the omecamtiv mecarbil group and 798 patients (19.4%) of the placebo group died from cardiovascular causes (HR = 1.01; 95% CI, 0.92–1.11). No significant difference was observed between groups in the change from baseline on the KCCQ total symptom score.

First hospitalization for HF exhibited a HR of 0.95 (95% CI, 0.87–1.03) for those in the omecamtiv mecarbil group compared with the placebo group, with death from any cause shown to be similar across both groups (HR = 1.00; 95% CI, 0.92–1.09). There was a 7% lower risk of a first HF event among patients administered omecamtiv mecarbil (n = 1177; 28.6%) compared with placebo (n = 1236; 30.1%), but this finding was not statistically significant (HR = 0.93; 95% CI, 0.86–1.00).

Researchers additionally were interested in examining the effects of omecamtiv mecarbil on vital signs, in which no difference was shown between groups in the change of systolic blood pressure between baseline and 24 or 48 weeks. Although, the change from baseline for the medican N-terminal pro-B–type natriuretic peptide level was shown to be 10% lower in the omecamtiv mecarbil group than in the placebo group.

The investigators noted that the drug was particularly effective for patients with lower ejection fraction.

“The benefit was consistent across most subgroups, but a possible heterogeneity of effect was suggested by a potentially greater treatment effect in patients with an ejection fraction of 28% or less than in those with an ejection fraction of more than 28%,” they wrote.

The latest research adds to the plethora of emerging medications in the treatment of HFrEF. In comparison with findings from the VICTORIA trial, which assessed the same primary outcome of a composite of a HF event or death from cardiovascular causes for vericiguat, an oral soluble guanylate cyclase stimulator, the relative risk reduction of 8% in the GALACTIC-HF trial is lower than that of vericiguat (10% relative risk reduction).

As with GALACTIC-HF, the VICTORIA trial found that results for vericiguat were different in some subgroups.

So, what distinguishable benefits may omecamtiv mecarbil provide patients with HFrEF?

Paul Heidenreich, MD, MS, professor of cardiovascular medicine at Stanford University, commented during the presentation that it “remains to be investigated and discussed about exactly where omecamtiv mecarbil will fit in.”

However, Heidenreich notes that there are several promising signs for omecamtiv mecarbil, particularly how it causes no reduction in blood pressure. “Often this is a major limiting factor for many patients with HF who cannot tolerate some of those other therapies–this might be an option.”


Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure. N Engl J Med. Published online November 13, 2020. doi:10.1056/NEJMoa2025797