Managing surgery in hemophilia with recombinant factor VIII Fc and factor IX Fc: Data on safety and effectiveness from phase 3 pivotal studies

Abstract

Abstract Background Surgical procedures impose hemostatic risk to people with hemophilia, which may be minimized by optimal factor (F) replacement therapy. Methods This analysis evaluates the efficacy and safety of extended half‐life factor replacement recombinant FVIII and FIX Fc fusion proteins (rFVIIIFc and rFIXFc) during surgery in phase 3 pivotal (A‐LONG/Kids A‐LONG and B‐LONG/Kids B‐LONG) and extension (ASPIRE and B‐YOND) studies. Dosing regimens were determined by investigators. Injection frequency, dosing, blood loss, transfusions, and hemostatic response were assessed. Results Forty‐five major (n = 31 subjects) and 90 minor (n = 70 subjects) procedures were performed in hemophilia A; 35 major (n = 22) and 62 minor (n = 37) procedures were performed in hemophilia B. Unilateral knee arthroplasty was the most common major orthopedic procedure (hemophilia A: n = 15/34; hemophilia B: n = 8/24). On the day of surgery, median total dose in adults/adolescents was 81 IU/kg for rFVIIIFc and 144 IU/kg for rFIXFc; most major procedures required ≤2 injections (including loading dose). Through days 1–14, most major procedures had ≤1 injection/day. Hemostasis was rated excellent (rFVIIIFc: n = 39/42; rFIXFc: n = 29/33) or good (n = 3/42; n = 4/33) in evaluable major surgeries, with blood loss comparable with subjects without hemophilia. Most minor procedures in adults/adolescents required one injection on the day of surgery, including median loading dose of 51 IU/kg (rFVIIIFc) and 80 IU/kg (rFIXFc). No major treatment‐related safety concerns were identified. No subjects developed inhibitors or serious vascular thromboembolic events. Conclusions rFVIIIFc and rFIXFc were efficacious and well tolerated for the management of perioperative hemostasis across a wide spectrum of major and minor surgeries in hemophilia.

Keywords

• factor IX fc fusion protein
• factor VIII Fc fusion protein
• hemophilia A
• hemophilia B
• recombinant fusion proteins
• safety