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

Abstract

The safety and efficacy of B-domain deleted recombinant factor VIII (BDDrFVIII) were evaluated in previously untreated patients (PUPs) with severe hemophilia A. In an open-label multicenter study, 101 PUPs received routine prophylactic and/or on-demand treatment with BDDrFVIII, including treatment related to surgery for 50 exposure days for up to 5 years. The pharmacokinetic measurements (ie, elimination half-life and in vivo mean recovery) assessed at baseline and 12 months were stable for BDDrFVIII over time. A total of 1,362 hemorrhages occurred. Ninety-two percent ( 1,258 1,362 ) of bleeding episodes resolved after three infusions or fewer. Of the 2,375 infusions rated by investigators, 93% ( 2,215 2,375 ) were rated as providing an “excellent” or “good” response. Twenty-seven patients received routine prophylactic treatment, which significantly reduced breakthrough bleeding episodes by twofold when compared with patients who were treated on-demand. Administration in conjunction with 40 surgical procedures showed no adverse effects, and the overall assessment was either “very useful” or “useful.” The mean dose was 56 IU/kg for routine primary prophylaxis and 53 IU/kg for on-demand therapy for bleeding episodes in patients who were assessed to be inhibitor-free at the time of infusion. Thirty-two percent of patients developed inhibitors. Of these, 16 patients were high responders (peak titer ≥ 5 Bethesda units [BU]). The inhibitor risk was comparable to that seen with full-length recombinant products. BDDrFVIII was found to be effective, safe, and well tolerated.