A new form of Filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans

Granulocyte colony-stimulating factor (G-CSF) has proven effective in the p rophylaxis of chemotherapy-induced neutropenia and as a mobilizer of periph eral blood progenitor cells. The longevity of G-CSF action is limited by it s removal from the body by two mechanisms. The first is thought to be media ted via receptors (receptor mediated clearance [RMC]) predominantly on neut rophils, the second process is likely the result of renal clearance. With t he intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has be en made by association of Filgrastim with poly(ethylene glycol). The desire d properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is sho wn here to sustain significantly elevated neutrophil counts in hematopoieti cally normal mice for 5 days. In neutropenic mite effects were noted for at least 9 days, accompanying a significant reduction in the duration of chem otherapy induced neutropenia. Normal human volunteers showed higher than ba seline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34(+) cel ls and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrasti m. These data indicate that SD/01 represents an efficacious novel form of F ilgrastim with actions sustained for between one and two weeks from a singl e injection. (C) 1999 International Society for Experimental Hematology. Pu blished by Elsevier Science Inc.