Amgen and Cytokinetics announced data from ATOMIC-AHF (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility inAcute Heart Failure), a Phase 2 study of omecamtiv mecarbil in patients with acute heart failure (AHF).
Omecamtiv mecarbil is a novel cardiac myosin activator that increases contractility in the absence of changes in intracellular calcium in cardiac myocytes.
ATOMIC-AHF was a randomized, double-blind, placebo-controlled clinical trial designed to evaluate an intravenous formulation ofomecamtiv mecarbil in 613 patients hospitalized with acute heart failure (AHF) in three sequential, ascending-dose cohorts. In each cohort, patients were randomized 1:1 to omecamtiv mecarbil or placebo.
The primary efficacy endpoint of this trial was to evaluate the effect of 48 hours of intravenous omecamtiv mecarbil compared to placebo on dyspnea in patients with left ventricular systolic dysfunction hospitalized for acute heart failure.
The omecamtiv mecarbil treatment groups were not statistically different in their 7-point Likert scale dyspnea symptom response rates compared to the pooled placebo group (P =0.33); therefore, the primary endpoint was not met. Omecamtiv mecarbil demonstrated favorable dose- and concentration-related trends (nominal P =0.025 and nominal P =0.007, respectively) on dyspnea response.
Improvement in dyspnea was observed in the highest omecamtiv mecarbil dose group when compared against its paired placebo group in the third cohort, with a dyspnea symptom response in 51% of patients on omecamtiv mecarbil vs. 37% on placebo, nominal P =0.03.
The incidence of worsening heart failure within seven days of initiating treatment was 17% in the pooled placebo group and was 13%, 8% and 9% on omecamtiv mecarbil in the first, second and third cohorts, respectively. Systolic ejection time, the echocardiographic signature of omecamtiv mecarbil, increased in a concentration-dependent manner.
Oral formulations of omecamtiv mecarbil are currently being evaluated in a Phase 2 trial known as COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure).
COSMIC-HF is a double-blind, randomized, placebo-controlled, multicenter, dose escalation study designed to evaluate the safety and efficacy of omecamtiv mecarbil in approximately 420 patients with chronic heart failure and left ventricular systolic dysfunction.
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