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Introduction: Recombinant factor IX Fc fusion protein (rFIXFc) has demonstrated efficacy for treatment of haemophilia B in the Phase 3 B‐LONG and Kids B‐LONG studies. However, long‐term rFIXFc safety and efficacy data have not yet been reported. Aim: To report long‐term rFIXFc safety and efficacy in subjects with haemophilia B. Methods: B‐YOND (NCT01425723) was an open‐label extension for eligibl previously treated subjects who completed B‐LONG or Kids B‐LONG. Subjects received ≥1 treatment regimen: weekly prophylaxis (WP), individualized interval prophylaxis (IP), modified prophylaxis or episodic treatment. Subjects could switch regimens at any time. The primary endpoint was inhibitor development. Results: Ninety‐three subjects from B‐LONG and 27 from Kids B‐LONG (aged 3‐63 years) were enrolled. Most subjects received WP (B‐LONG: n = 51; Kids B‐LONG: n = 23). For subjects from B‐LONG, median (range) treatment duration was 4.0 (0.3‐5.4) years and median (range) number of exposure days (EDs) was 146 (8‐462) EDs. Corresponding values for paediatric subjects were 2.6 (0.2‐3.9) years and 132 (50‐256) EDs. No inhibitors were observed (0 per 1000 subject‐years; 95% confidence interval, 0‐8.9) and the overall rFIXFc safety profile was consistent with prior studies. Annualized bleed rates remained low and extended‐dosing intervals were maintained for most subjects. Median dosing interval for the IP group was approximately 14 days for adults and adolescents (n = 31) and 10 days for paediatric subjects (n = 5). Conclusions: B‐YOND results confirm the long‐term (up to 5 years, with cumulative duration up to 6.5 years) well‐characterized safety and efficacy of rFIXFc treatment for haemophilia B. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy and safety of recombinant factor VIII Fc fusion protein (rFVIIIFc) as an extended half‐life treatment for severe haemophilia A were demonstrated in the Phase 3 A‐LONG and Kids A‐LONG studies. Eligible subjects who completed A‐LONG and Kids A‐LONG could enrol in ASPIRE (NCT01454739), an open‐label extension study. Aim: To report the long‐term safety and efficacy of rFVIIIFc in subjects with severe haemophilia A who enrolled in ASPIRE. Methods: Previously treated subjects received one or more of the following regimens: individualized prophylaxis (IP), weekly prophylaxis, modified prophylaxis or episodic treatment. Subjects could switch treatment regimen at any time. The primary endpoint was inhibitor development. Results: A total of 150 subjects from A‐LONG and 61 subjects from Kids A‐LONG enrolled in ASPIRE. Most subjects received the IP regimen (A‐LONG: n = 110; Kids A‐LONG: n = 59). Median (range) treatment duration in ASPIRE for subjects from A‐LONG and Kids A‐LONG was 3.9 (0.1‐5.3) years and 3.2 (0.3‐3.9) years, respectively. No inhibitors were observed (0 per 1000 subject‐years; 95% confidence interval, 0‐5.2) and the overall rFVIIIFc safety profile was consistent with prior studies. For subjects on the IP regimen, annualized bleed rates (ABR) remained low (median overall ABR for adults and adolescents was <1.0) and extended‐dosing intervals were maintained (median of 3.5 days) for the majority of subjects in ASPIRE. Conclusion: ASPIRE results, which include up to 5 years of follow‐up data, confirm earlier reports on the consistent and well‐characterized safety and efficacy of rFVIIIFc treatment for severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: Rurioctocog alfa pegol (BAX 855, TAK‐660) is a PEGylated, full‐length, recombinant factor VIII (rFVIII) with extended half‐life developed from unmodified rFVIII (antihaemophilic factor [recombinant]). Aim: To determine the perioperative haemostatic efficacy and safety of rurioctocog alfa pegol in male previously treated patients (PTPs) with severe haemophilia A. Methods: This multicentre, single‐arm, phase III study included PTPs who were to undergo major or minor elective or minor emergency surgical, dental or other invasive procedures. Rurioctocog alfa pegol dose and frequency were individualized based on patients' pharmacokinetic profiles for major surgeries and by rurioctocog alfa pegol incremental recovery for minor surgeries. Haemostatic efficacy was assessed using the Global Haemostatic Efficacy Assessment score. Results: Twenty‐one patients aged 16‐61 years underwent 21 major and five minor surgeries. For all 24 evaluable surgeries, overall haemostatic efficacy was rated as excellent and blood loss comparable to that expected in non‐haemophilic patients. No blood transfusions were required intraoperatively but were administered postoperatively for four surgeries in three patients. Five injury‐related postoperative bleeding episodes occurred in five patients, of which two required additional rurioctocog alfa pegol treatment. Two non‐serious adverse events of mild severity (increased ALT level and headache) were considered possibly related to rurioctocog alfa pegol. There were no deaths or treatment‐related serious adverse events. No patients developed inhibitory antibodies to FVIII or persistent IgG‐ or IgM‐binding antibodies to FVIII, PEG‐FVIII or PEG. Conclusion: Rurioctocog alfa pegol was well tolerated and effective for perioperative use in patients with haemophilia A and showed no signs of immunogenicity. [ABSTRACT FROM AUTHOR]

Introduction BAX 855 is a pegylated full-length recombinant factor VIII ( rFVIII) with an extended half-life, built on a licensed rFVIII ( ADVATE®). BAX 855 demonstrated efficacy and safety in prophylaxis and the treatment of bleeding episodes in previously treated patients (PTPs) with severe haemophilia A. Aim This phase 3 surgery study evaluates the haemostatic efficacy and safety of BAX 855 for perioperative haemostasis in PTPs with severe haemophilia A undergoing surgery. Methods Elective procedures were prospectively classified as major or minor. The dose and frequency of BAX 855 administered perioperatively were to be guided by each patient's pharmacokinetic profile for major procedures or BAX 855 incremental recovery for minor procedures. Haemostatic efficacy was evaluated using a predefined scale. Blood loss was compared to the expected average and maximum blood loss predicted preoperatively. Results A total of 15 male patients (aged 19-52 years) underwent 15 procedures (11 major and four minor). The overall intra- and perioperative haemostatic efficacy of BAX 855 was 'excellent' in all 15 subjects (100%). Postoperatively, evaluated at postoperative Day 1, all treatments were 'excellent' except for one minor (dental) procedure which was rated 'good'. No related adverse events, allergic reactions, thrombotic events, nor signs of immunogenicity in terms of induction of binding antibodies to FVIII, PEG or PEG- VIII, or FVIII inhibitors were observed. Conclusion These results demonstrate that BAX 855 is safe and haemostatically effective in patients with severe haemophilia A undergoing surgery. [ABSTRACT FROM AUTHOR]

Factor VIII Inhibitor Bypassing Activity ( FEIBA) can effectively achieve haemostasis in haemophilia patients with inhibitors. Further evaluation of FEIBA in surgical settings is of significant interest considering the relatively limited prospective data published to date. The aim of the study is to evaluate the perioperative efficacy and safety of FEIBA in haemophilia patients with inhibitors. Haemophilia patients with inhibitors who underwent surgical procedures and received FEIBA for perioperative haemostatic control were prospectively enrolled in an open-label, noninterventional, postauthorization study [ SURgical interventions with FEIBA ( SURF)]. Outcome measures included haemostatic efficacy, safety, FEIBA exposure and blood loss associated with the perioperative use of FEIBA. Thirty-five surgical procedures were performed at 19 centres worldwide in patients with congenital haemophilia A, congenital haemophilia B, or acquired haemophilia A. Haemorrhagic risk was severe in 37.1% (13 of 35) of the procedures, moderate in 25.7% (9 of 35) and mild in 37.1% (13 of 35). One moderate risk surgery was excluded from the efficacy analyses because it did not meet all protocol requirements. Haemostasis was judged to be 'good' or 'excellent' in 91.2% (31 of 34) of surgical procedures and 'fair' in 8.8% (3 of 34). Among the 12 adverse events, three were serious adverse events ( SAEs), two of which were unrelated to FEIBA therapy; one SAE, a clot in an arteriovenous fistula, was deemed to be possibly related to therapy. This prospective investigation confirms that FEIBA can be safely and effectively used when performing surgical procedures in haemophilia patients with inhibitors. [ABSTRACT FROM AUTHOR]