Peginesatide in patients with anemia undergoing hemodialysis.
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].).
Hofstra North Shore-LIJ School of Medicine, Great Neck, NY 11021, USA. sfishbane@nshs.edu
Steven
S
Fishbane
Brigitte
B
Schiller
Francesco
F
Locatelli
Adrian C
AC
Covic
Robert
R
Provenzano
Andrzej
A
Wiecek
Nathan W
NW
Levin
Mark
M
Kaplan
Iain C
IC
Macdougall
Carol
C
Francisco
Martha R
MR
Mayo
Krishna R
KR
Polu
Anne-Marie
AM
Duliege
Anatole
A
Besarab
D000368:Aged; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000906:Antibodies / Q000097:blood; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000009:adverse effects / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000401:mortality / Q000628:therapy*
D000906:Antibodies; D006397:Hematinics; D006454:Hemoglobins; D010455:Peptides; D004921:Erythropoietin; C556270:peginesatide