Pharmacokinetics, prophylactic effects, and safety of a new recombinant FVIII formulated with sucrose (BAY 14-2222) in Japanese patients with hemophilia A.

Abstract

A clinical trial of BAY 14-2222, a recombinant factor VIII preparation (rFVIII) manufactured by new purification and formulation processes using sucrose as a stabilizer instead of human serum albumin, was performed in 5 previously treated Japanese patients with severe hemophilia A. In stage I, a single dose of BAY 14-2222 and Kogenate (a currently licensed rFVIII preparation) was administered alternately in the same patients to compare the pharmacokinetics of the 2 compounds using FVIII:C (FVIII clotting activity) as the measure of plasma drug levels. The normalized area under the curve (AUCnorm) and normalized maximal concentration (Cmax,norm) were slightly lower following the administration of BAY 14-2222 than those after the administration of Kogenate (ratio of BAY 14-2222/Kogenate:AUCnorm = 0.88, P = .050; and Cmax,norm = 0.87, P = .041). However, the biological half-life (t1/2) did not differ significantly between the 2 preparations (13.96 +/- 4.18 vs. 13.48 +/- 2.40 hours). The in vivo recovery of FVIII was 67.9 +/- 11.3% after the administration of BAY 14-2222 and 74.4 +/- 5.3% after the administration of Kogenate. In stage II, BAY 14-2222 was administered regularly to the 5 patients with hemophilia at single doses of 20 to 40 IU/kg 3 times weekly for 4 weeks, and its prophylactic effect on bleeding was evaluated. Results indicated that BAY 14-2222 has a good preventive effect on bleeding. Sixty-six infusions were performed in stages I and II of this trial, and no adverse reactions related to BAY 14-2222 were observed. In addition, there were no FVIII inhibitors or antibodies to foreign proteins detected. The trial confirmed that BAY 14-2222 is similar to Kogenate with respect to t1/2 and the in vivo recovery of FVIII:C and that periodic infusions for 4 weeks can be well tolerated. In addition, it was shown that BAY 14-2222 is effective in preventing bleeding. Thus it is expected that BAY 14-2222 will exhibit a hemostatic effect comparable to that of Kogenate in patients with hemophilia A.