THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif., Sept. 3, 2013 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and Cytokinetics Incorporated (NASDAQ: CYTK) today announced the first presentation of data from the ATOMIC-AHF ( Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure) study at the ESC Congress 2013, organized by the European Society of Cardiology, in Amsterdam. ATOMIC-AHF was a randomized, double-blind, placebo-controlled Phase 2 study that enrolled 613 patients hospitalized with acute heart failure (AHF) treated for 48 hours with omecamtiv mecarbil or placebo and designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and potential efficacy of an intravenous formulation of omecamtiv mecarbil in patients with AHF. The study did not meet its primary endpoint of dyspnea (shortness of breath) response as measured by the 7-point Likert scale through 48 hours ( p=0.33) but showed favorable dose and concentration-related trends on dyspnea response.
ATOMIC-AHF enrolled three, sequential, dose escalation cohorts of patients treated for 48 hours with omecamtiv mecarbil or placebo. The primary efficacy endpoint in ATOMIC-AHF was dyspnea symptom response. Secondary endpoints included other clinical and pharmacodynamic (echocardiographic) effects including death or worsening heart failure within seven days. 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 (dyspnea symptom response in 51 percent of subjects on omecamtiv mecarbil versus 37 percent on placebo, nominal p=0.03). The incidence of worsening heart failure within seven days of initiating treatment was 17 percent in the pooled placebo group and was 13 percent, 8 percent and 9 percent 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.
Rates of adverse events (AEs), serious AEs, adjudicated deaths and hospitalizations were similar between omecamtiv mecarbil and placebo groups. There were seven post-randomization myocardial infarctions in the omecamtiv mecarbil treated groups compared with three in the placebo groups (2.3 percent vs. 1.0 percent, respectively). However, there was no relationship between the maximum increase from the baseline troponin (a biomarker specific for cardiac muscle damage) and increasing plasma concentrations of omecamtiv mecarbil. Omecamtiv mecarbil was not associated with an increased incidence of tachyarrhythmias nor were heart rate or blood pressure adversely affected.
"Although ATOMIC-AHF did not achieve its primary efficacy endpoint, we are encouraged by the data from this study," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. " Omecamtiv mecarbil is a unique investigational therapy for patients with acute and chronic heart failure. We look forward to the data from the COSMIC-HF study, which together with the data from ATOMIC-AHF will inform our decision on whether to progress omecamtiv mecarbil into Phase 3 clinical trials.""We are pleased with the results from ATOMIC-AHF," stated Robert I. Blum, President and CEO at Cytokinetics. "This novel mechanism drug candidate has consistently been associated with dose-related and plasma concentration-related pharmacodynamic and other effects in a robust program of Phase 1 and Phase 2 clinical trials. We look forward to results from COSMIC-HF and the potential progression of omecamtiv mecarbil in development."