Peginesatide is a synthetic, dimeric peptide that is covalently linked to 
polyethylene glycol (PEG). The amino acid sequence of peginesatide is unrelated 
to that of erythropoietin (EPO) and is not immunologically cross-reactive with 
EPO. Peginesatide binds to and activates the human EPO receptor, stimulating the 
proliferation and differentiation of human red cell precursors in vitro in a 
manner similar to other EPO-stimulating agents (ESAs). In Phase II and III 
studies in dialysis and predialysis patients, peginesatide administered once 
monthly was as effective as epoetin alfa given thrice weekly (dialysis patients) 
or darbepoetin given once weekly (nondialysis patients), in correcting anemia of 
chronic kidney disease as well as maintaining hemoglobin within the desired 
target range. In the dialysis population, the reported side-effect profile of 
peginesatide was comparable to that known with other marketed ESAs. In the 
nondialysis studies, compared with those treated with darbepoetin, patients 
treated with peginesatide experienced a higher adverse-effect profile. 
Peginesatide is likely to be licensed for treatment of renal anemia in dialysis 
patients and not in nondialysis patients. Despite this limitation, peginesatide 
is likely to prove valuable in treating dialysis patients because of its 
infrequent mode of administration, thereby allowing for a reduced number of 
injections, with associated better compliance, reduced cold storage requirement, 
and improved stock accountability. PEGylated therapeutic proteins can elicit 
immunological response to the PEG moiety of the therapeutic complex. Only 
long-term experience and post-marketing surveillance will address whether this 
immunological response will have any impact on the clinical efficacy or safety 
of peginesatide in clinical practice.