Key Points A novel recombinant factor VIII with prolonged half-life, rFVIIIFc, was developed to reduce prophylactic injection frequency. rFVIIIFc was well-tolerated in patients with severe hemophilia A, and resulted in low bleeding rates when dosed 1 to 2 times per week.

Prophylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.).

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SummaryIn the phase 3 B-LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half-life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately-severe to severe haemophilia B. In this B-LONG sub-analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator-determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, 2 weeks-12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85Á7%), haemostasis from the pre-surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R 2 = 0Á9586, P < 0Á001) between observed and population pharmacokinetic model-predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.

Essentials• Congenital afibrinogenemia causes a potentially lifethreatening bleeding and clotting tendency.• Two human fibrinogen concentrates (HFCs) were compared in a randomized pharmacokinetic study.• Bioequivalence was not shown for AUC norm , which was significantly larger for the new HFC.• Increases in clot strength were comparable, and no thromboses or deaths occurred in the study. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Journal of Thrombosis and Haemostasis, 16: 253-261 DOI: 10.1111/jth.13923 increases in clot strength were comparable between concentrates.