Cytokinetics, Incorporated announced new data at AHA meeting from post-hoc analyses of GALACTIC-HF phase III trial of omecamtiv mecarbil for cardiovascular outcomes.

“These analyses reinforce the potential treatment benefit of omecamtiv mecarbil in patients from GALACTIC-HF who are at higher risk, such as older patients or those with a recent ventricular arrhythmia,” said Stuart Kupfer, M.D., Senior Vice President, Chief Medical Officer. “As we prepare for the start of COMET-HF, the confirmatory Phase III clinical trial of omecamtiv mecarbil, we look forward to evaluating its potential to reduce the risk of adverse heart failure outcomes across the spectrum of these very high-risk patients failing guideline-directed medical therapy.”

Treatment with Omecamtiv Mecarbil Reduced Risk of the Primary Composite Endpoint in Patients with Severe Heart Failure Independent of Age; A post-hoc analysis from GALACTIC-HF supports the potential efficacy of omecamtiv mecarbil irrespective of age, including in patients with severe heart failure. Of the 8,232 patients included in the analysis, patients were on average 64.5 years old, with 54.5% aged ≥65 years. At baseline, patients aged ≥65 years were more likely to be women, have atrial fibrillation or flutter, have worse New York Heart Association (NYHA) Functional Class and have higher NT-proBNP as compared to patients aged <65 years. Over a median follow-up period of 21.8 months, the primary composite endpoint of cardiovascular death or heart failure events occurred at a rate of 21.4 per 100 patient years among patients <65 years, and 28.8 per 100 patient years in patients ≥65 years. In the overall study population, 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). Additionally, 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 Arrythmias Associated with Adverse Clinical Outcomes in Patients with Heart Failure and Reduced Ejection Fraction; Treatment with Omecamtiv Mecarbil Reduces Risk of Ventricular Arrythmias in Patients with Severely Reduced LVEF; A second post-hoc analysis from GALACTIC-HF investigated clinical consequences of ventricular arrhythmias (VA) in the patients studied in GALACTIC-HF. Of the 8,232 patients enrolled in GALACTIC-HF, following an occurrence of VA, there was 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 was not associated with an increase in the occurrence of VA and the occurrence of VA in participants treated with omecamtiv mecarbil did not impart worse prognosis than those with VA compared to placebo. Of note, 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, Figure 1). Overall, these findings support the safety of omecamtiv mecarbil with regards to VA as well as a potential benefit in patients with severely reduced LVEF and are consistent with the findings of increased treatment effect of omecamtiv mecarbil in patients with severely reduced LVEF.

About Heart Failure with Severely Reduced Ejection Fraction; Heart failure is a grievous condition that affects more than 64 million people worldwide about half of whom have reduced left ventricular function. It is the leading cause of hospitalization and readmission in people age 65 and older. By 2029 is it estimated that 2.8 million people in the U.S. will have heart failure with severely reduced ejection fraction, characterized as heart failure with reduced ejection fraction (HFrEF) <30%, and 840,000 people will have severely reduced ejection fraction with other features indicative of high risk heart failure. Patients with high risk heart failure with severely reduced ejection fraction account for approximately 60% of all HFrEF hospitalizations, with 35% of patients re-hospitalized within a year.