Peginesatide is a PEGylated, investigational, peptide-based 
erythropoiesis-stimulating agent (ESA) that was designed and engineered to 
stimulate specifically the erythropoietin receptor dimer that governs 
erythropoiesis. Clinical use of peginesatide is anticipated to result in chronic 
dosing in chronic kidney disease (CKD) patients, and the nonclinical data to 
support development should include an evaluation of carcinogenic potential 
evaluation. Peginesatide was not mutagenic or clastogenic in a standard 
genotoxicity battery of tests. Doses for a rasH2 transgenic mouse 
carcinogenicity assay were defined in a 28-day study in the wild-type 
littermates of the rasH2 transgenic mouse strain, using intravenous doses of 
1-25 mg/kg on days 1 and 22. The findings were consistent with exaggerated 
pharmacology, including polycythemia, with associated increases in hemoglobin 
level and extramedullary hematopoiesis and bone marrow hypercellularity.