Preclinical Safety Pharmacology of Baxter’s Longer Acting rFVIII (BAX 855)

Abstract 4357

Baxter has developed a PEGylated recombinant human factor VIII conjugate by modifying the FVIII molecule with polyethylene glycol (PEGylation). The product is derived from a CHO cell line using a plasma-protein-free method and a virus inactivation step. The objective of this preclinical study-program was to evaluate the safety of Baxter’s longer acting rFVIII in different species. The thrombogenic potential of Baxter’s longer acting rFVIII was evaluated in the rabbit stasis model developed by Wessler. Two lots of Baxter’s longer acting rFVIII were used to demonstrate consistent safety between different batches. Advate served as the control item. Baxter’s longer acting rFVIII was not thrombogenic in this preclinical model at a dose of 900 U/kg. There was no evidence of thrombogenic potential after intravenous treatment with either the test item or Advate, the active reference item. The effects of Baxter’s longer acting rFVIII on body temperature, heart rate, blood pressure, respiratory variables or QT, QTcf, PR and/or QRS intervals and respiratory system (intra-thoracic pressure) was evaluated in eight male, conscious telemetered cynomolgus monkeys. Baxter’s longer acting rFVIII was given at 150 and 600 U/kg/day to male monkeys by intravenous administration. Baxter’s longer acting rFVIII did not cause any adverse clinical, respiratory or cardiovascular effects and was very well tolerated at all dose levels tested. In conclusion, Baxter’s longer acting rFVIII did not cause any thrombocenic events or adverse clinical, respiratory or cardiovascular effects and was very well tolerated at all dose levels.