BACKGROUND: Peginesatide, a synthetic peptide-based erythropoiesis-stimulating 
agent (ESA), is a potential therapy for anemia in patients with advanced chronic 
kidney disease.
METHODS: We conducted two randomized, controlled, open-label studies (EMERALD 1 
and EMERALD 2) involving patients undergoing hemodialysis. Cardiovascular safety 
was evaluated by analysis of an adjudicated composite safety end point--death 
from any cause, stroke, myocardial infarction, or serious adverse events of 
congestive heart failure, unstable angina, or arrhythmia--with the use of pooled 
data from the two EMERALD studies and two studies involving patients not 
undergoing dialysis. In the EMERALD studies, 1608 patients received peginesatide 
once monthly or continued to receive epoetin one to three times a week, with the 
doses adjusted as necessary to maintain a hemoglobin level between 10.0 and 12.0 
g per deciliter for 52 weeks or more. The primary efficacy end point was the 
mean change from the baseline hemoglobin level to the mean level during the 
evaluation period; noninferiority was established if the lower limit of the 
two-sided 95% confidence interval was -1.0 g per deciliter or higher in the 
comparison of peginesatide with epoetin. The aim of evaluating the composite 
safety end point in the pooled cohort was to exclude a hazard ratio with 
peginesatide relative to the comparator ESA of more than 1.3.
RESULTS: In an analysis involving 693 patients from EMERALD 1 and 725 from 
EMERALD 2, peginesatide was noninferior to epoetin in maintaining hemoglobin 
levels (mean between-group difference, -0.15 g per deciliter; 95% confidence 
interval [CI], -0.30 to -0.01 in EMERALD 1; and 0.10 g per deciliter; 95% CI, 
-0.05 to 0.26 in EMERALD 2). The hazard ratio for the composite safety end point 
was 1.06 (95% CI, 0.89 to 1.26) with peginesatide relative to the comparator ESA 
in the four pooled studies (2591 patients) and 0.95 (95% CI, 0.77 to 1.17) in 
the EMERALD studies. The proportions of patients with adverse and serious 
adverse events were similar in the treatment groups in the EMERALD studies. The 
cardiovascular safety of peginesatide was similar to that of the comparator ESA 
in the pooled cohort.
CONCLUSIONS: Peginesatide, administered monthly, was as effective as epoetin, 
administered one to three times per week, in maintaining hemoglobin levels in 
patients undergoing hemodialysis. (Funded by Affymax and Takeda Pharmaceutical; 
ClinicalTrials.gov numbers, NCT00597753 [EMERALD 1], NCT00597584 [EMERALD 2], 
NCT00598273 [PEARL 1], and NCT00598442 [PEARL 2].).