The Induction of Prolonged Myelopoietic Effects in Monkeys by GW003, A Recombinant Human Granulocyte Colony-Stimulating Factor Genetically Fused to Recombinant Human Albumin.

GW003, a genetic fusion protein of human serum albumin and granulocyte colony-stimulating factor ( G- CSF), was developed based on a novel strategy for producing long-acting proteins. The purpose of this study was to evaluate the hematologic, pharmacokinetic, and toxicokinetic effects of GW003 on cynomolgus monkeys. We show that following a single subcutaneous administration of GW003, the absolute neutrophil count increased significantly compared with monkeys that received only the vehicle, and the magnitude of the neutrophilic response to GW003 was dose dependent. After an injection at equal molar dose, the clearance of GW003 in the monkeys was approximately fourfold slower, and the terminal half-life ( T1/2) was fivefold longer than the corresponding values for recombinant methionyl human G- CSF. Interestingly, both the clearance and T1/2 decreased with increasing doses of GW003, and much faster elimination was observed after multidose exposure. In toxicokinetic studies, the serum concentration of GW003 after the eighth injection was much lower than it was after the first injection, and a neutralizing antibody against G- CSF was found to have a dose-dependent effect upon the treatment groups. Overall, the favorable pharmacokinetic and pharmacodynamic properties supported the selection and development of GW003 as a promising candidate for neutropenia therapy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:760-767, 2015 [ABSTRACT FROM AUTHOR]