Preclinical Safety of Baxter's Recombinant Factor IX

Abstract 4654

Baxter has developed a rFIX product which is produced by a genetically engineered Chinese hamster ovary (CHO) cell line in a cell culture medium free from any animal or human proteins. The objective of this preclinical study-program was to evaluate the safety of Baxter's rFIX in different species.

The preclinical program included studies on established models of general safety pharmacology (conscious, telemetered cynomolgus monkey), thrombogenicity (rabbit, Wessler test), single and repeated dose toxicity (mouse, rat, cynomolgus monkey), local tolerance (rabbit), and comparative immunogenicity (mouse, rat, cynomolgus monkey). Commercially available licensed rFIX and pdFIX served as active reference items.

Thrombogenicity studies showed no thrombogenic potential of Baxter's rFIX. General safety pharmacology revealed no adverse effects on clinical signs, cardiovascular or respiratory variables. Single dose toxicity studies in mice, administered at doses of up to 7500 IU/kg BW, and repeated administration of Baxter's rFIX in rats and cynomolgus monkeys, administered doses of up to 750 IU/kg, confirmed the safety of the new product. Furthermore, Baxter's rFIX was well tolerated at the injection site after intravenous injection. No differences in immunogenicity between Baxter's rFIX and the reference items were revealed by comparative immunology studies.

This good safety profile of Baxter's rFIX was the basis for proceeding with human trials, which have recently been initiated.