Clinical evaluation of B-domain deleted recombinant factor VIII in previously treated patients.

The pharmacokinetics, safety, and efficacy of B-domain deleted recombinant factor VIII (BDDrFVIII) were evaluated in patients with hemophilia A. In an initial 12-month study with subsequent yearly extensions over a 5-year period, 113 previously treated patients (PTPs) received on-demand and/or prophylactic treatment with BDDrFVIII, including treatment during surgery, if required. Half-life and recovery of factor VIII activity remained unchanged over the study period. The mean elimination half-life was 10.5 +/- 2.6 hours at baseline and 10.4 +/- 3.3 hours at month 12. A total of 7,310 hemorrhages occurred for patients who received on-demand treatment, with 71% resolving after a single infusion. Of the 11,655 rated infusions given for hemorrhages, 92% were rated by investigators and patients as providing an "excellent" or "good" response. These results are consistent with efficacy data from other trials using recombinant factor VIII products. During the prophylactic period, 12% of patients experienced no bleeding episodes, and 17% of the patients had no on-demand treatment. The mean dose was 28 IU/kg for prophylactic treatment and 30 IU/kg for on-demand treatment. The efficacy of administering BDDrFVIII in conjunction with surgery was assessed to be "very useful" or "useful" in all cases. Few adverse events were reported, and only one patient developed inhibitors to factor VIII activity. The results show that BDDrFVIII provides a safe and effective treatment of hemophilia A when given as on-demand therapy, in routine or intermittent prophylaxis, or during surgery.