Omecamtiv mecarbil: Phase IIb data

The double-blind, international Phase IIb ATOMIC-AHF trial in 613 patients with left ventricular systolic dysfunction hospitalized for acute heart failure showed that omecamtiv mecarbil given as a 48-hour IV infusion missed the primary endpoint of improving dyspnea symptom response rate as measured by a 7-point Likert scale vs. placebo (p=0.33). The trial protocol specified that the primary endpoint compare pooled data from all 3 omecamtiv mecarbil arms to pooled data from patients receiving placebo in the 3 cohorts. Patients received placebo or omecamtiv mecarbil to a target plasma concentration of 115, 230 or 310 ng/mL.

A supplemental analysis of the primary endpoint showed that high-dose omecamtiv mecarbil significantly improved dyspnea symptom response rate compared to the placebo arm for only the high-dose cohort (51% vs. 37%, p=0.03). Low- (42% vs. 41%) and mid-dose (47% vs. 46%) omecamtiv mecarbil did not significantly improve response rates compared to their individual placebo arms. Responders were defined as minimally, moderately or markedly better at 6 hours and moderately or markedly better at 24 and 48 hours without worsening heart failure or death for any cause by 48 hours. ...