Cytokinetics presented new data from post-hoc analyses of the GALACTIC-HF trial, a Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil, at the American Heart Association Scientific Sessions 2024 in Chicago, IL. The analyses suggest potential benefits in high-risk heart failure patients, irrespective of age and in those with ventricular arrhythmias and severely reduced left ventricular ejection fraction (LVEF).
Omecamtiv Mecarbil's Impact on Severe Heart Failure Across Age Groups
The post-hoc analysis of 8,232 patients from the GALACTIC-HF trial showed that omecamtiv mecarbil's efficacy is consistent across different age groups, including older patients with severe heart failure. The study population had an average age of 64.5 years, with 54.5% being 65 years or older. Older patients were more likely to be women, have atrial fibrillation or flutter, have worse NYHA Functional Class, and higher NT-proBNP levels.
Over a median follow-up of 21.8 months, the primary composite endpoint of cardiovascular death or heart failure events occurred at rates of 21.4 and 28.8 per 100 patient years in patients younger and older than 65 years, respectively. The treatment effect of omecamtiv mecarbil was similar across age groups (interaction p=0.73). In patients with severe heart failure, omecamtiv mecarbil reduced the risk for the primary outcome independent of age group (HR 0.77; 95% CI, 0.64-0.92 and HR 0.83; 95% CI, 0.71-0.97 for patients <65 years and ≥65 years respectively; interaction p=0.72). These relative risk reductions were associated with large absolute risk reductions (8.6 and 7.9, respectively). Adverse events of special interest, such as ventricular arrhythmias (VA) and myocardial ischemic events, were similar between omecamtiv mecarbil and placebo in both age groups.
Ventricular Arrhythmias and Reduced LVEF
Another post-hoc analysis investigated the clinical consequences of ventricular arrhythmias (VA) in GALACTIC-HF patients. The occurrence of VA was associated with a significantly higher risk of the primary endpoint of cardiovascular death or heart failure events (HR 1.67; 95% CI 1.42-1.97; p<0.001) and all-cause mortality (HR 2.07; 95% CI 1.77-2.42; p<0.001).
Treatment with omecamtiv mecarbil did not increase the occurrence of VA, and the occurrence of VA in participants treated with omecamtiv mecarbil did not impart a worse prognosis than those with VA compared to placebo. Participants with lower LVEF had an increased risk of VA, and in those participants, treatment with omecamtiv mecarbil appeared to reduce the risk for the composite outcome of VA, cardiac arrest, and sudden death (LVEF ≤28%, HR 0.77, 95% CI 0.63-0.94; p=0.009).
Ongoing Development: COMET-HF Trial
Cytokinetics is preparing to start COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a confirmatory Phase 3 clinical trial in patients with symptomatic heart failure with severely reduced ejection fraction, expected to start in Q4 2024. This trial aims to further evaluate omecamtiv mecarbil's potential to reduce adverse heart failure outcomes in high-risk patients failing guideline-directed medical therapy.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator designed to directly target the contractile mechanisms of the heart. It increases the number of active actin-myosin cross bridges during each cardiac cycle, augmenting impaired contractility associated with heart failure with reduced ejection fraction (HFrEF).
