Hematide is a synthetic PEGylated peptidic
erythropoiesis stimulating agent (ESA) that is presently being developed for the correction of
anemia in patients with
chronic renal failure. Unlike currently marketed ESAs,
Hematide does not possess any sequence homology to
erythropoietin (EPO) and has not elicited moribund immune responses in animal safety studies thereby allowing the generation of a robust safety package. Animals administered marketed ESAs develop anti-EPO
antibodies that null the effect of the administered ESA and neutralize endogenous EPO, resulting in severe
anemia that precludes the interpretation of chronic safety studies. The primary objective of this study is to determine whether
Hematide-specific
antibodies are generated when male monkeys are exposed to high
Hematide doses (10 mg/kg, intravenous [IV] and subcutaneous [SC]) administered at frequent dosing intervals (every two weeks) for a total of 9 doses; secondary objectives are to evaluate whether developed
antibodies impact pharmacokinetics (PK) and pharmacology. In this study, no
Hematide-specific
antibodies were detected.
Hematide exhibits a prolonged plasma half-life and slow clearance by either IV or SC administration.
Hematide induced significant erythropoiesis with
reticulocytosis and subsequent increases in red blood cells, hematocrit and
hemoglobin (Hgb) levels. No erythropoietic differences were noted between the IV and the SC dosed groups with mean +/- SD Hgb levels of 20.9 +/- 2.5 and 20.3 +/- 2.1 g/dL, respectively, occurring on Day 48, corresponding to Hgb increases of 6.5 and 6.7 g/dL, respectively, over pre-dose levels. In conclusion,
Hematide is a potent
erythropoiesis stimulating agent that exhibits plasma persistence in monkeys. Similar erythropoietic responses were produced following IV and SC administration. The absence of antibody development suggests that
Hematide, at the doses and regimen described, has a low immunogenic potential in cynomolgus monkeys.