Safety and efficacy of turoctocog alfa (NovoEight^®) during surgery in patients with haemophilia A: results from the multinational guardian^™ clinical trials

Abstract

Recombinant factor VIII (rFVIII) products provide a safe and efficacious replacement therapy for prevention and treatment of bleeding episodes in patients with haemophilia A. The present investigations from the multinational, open-label guardian™ clinical trials assessed the haemostatic response of turoctocog alfa (NovoEight®), a rFVIII product, in patients with severe haemophilia A (FVIII ≤ 1%) undergoing surgery. All patients had a minimum of 50 exposure days to any FVIII product prior to surgery and no history of inhibitors. A total of 41 procedures (13 orthopaedic, 19 dental and 9 general) were performed in 33 patients aged 4–59 years. Of the 41 procedures, 15 were major surgeries in 13 patients and 26 were minor surgeries in 21 patients. The success rate for haemostatic response was 100% (success was defined as ‘excellent’ or ‘good’ haemostatic outcome). Turoctocog alfa consumption on the day of surgery ranged from 27 to 153 IU kg−1. The mean daily dose declined over time, while retaining adequate FVIII coverage as measured by trough levels. Overall, no safety issues were identified. No thrombotic events were observed and none of the patients developed FVIII inhibitors. In conclusion, the present results show that turoctocog alfa was effective in controlling blood loss by obtaining a sufficient haemostatic response in patients with severe haemophilia A undergoing surgery.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

“…For turoctocog alfa, intraoperative hemostasis was reported as excellent in 62% and good in 38% of 13 patients undergoing 15 procedures. 7,20 For personal use only. on May 10, 2018. by guest www.bloodjournal.org From Dosing in our study was at the investigators' discretion with a recommendation to start prophylaxis with a dose between 20 to 40 IU/kg rVIII-SingleChain every second day or 20 to 50 IU/kg 2 to 3 times per week.…”

First report on the safety and efficacy of an extended half‐life glycoPEGylated recombinant FVIII for major surgery in severe haemophilia A

“…In a study evaluating B‐domain‐deleted rFVIII (BDD‐rFVIII; Xyntha ® , Wyeth BioPharma Division of Wyeth Pharmaceuticals Inc., Philadelphia, PA, USA) for major (mostly orthopaedic) surgical procedures, the median dose was 25.5 (range, 8.4–72.9) IU kg −1 per infusion over a median of 43 (range, 16–72) infusions during the perioperative period . More recently, consumption of turoctocog alfa (NovoEight ® , Novo Nordisk A/S, Bagsværd, Denmark) on the day of surgery was reported to be 27–153 IU kg −1 for major procedures; the mean daily dose per patient declined over time from approximately 80 IU kg −1 to approximately 60 IU kg −1 for the first six postoperative days . Finally, in a study of unmodified, full‐length rFVIII (BAY 81‐8973), the median nominal dose on the day of major surgical procedures was 107.5 IU kg −1 , and the total dose range was 59.5–207.3 IU kg −1 .…”

“…Patients with severe haemophilia A experience recurrent spontaneous bleeding episodes , most of which occur in the joints leading to chronic arthropathy. Orthopaedic surgical procedures are often considered in such patients, with the aim of relieving pain and/or restoring joint function . Many non‐orthopaedic surgeries are also able to be performed in patients with haemophilia, including elective procedures and acute/emergency surgeries that may be required, for example, due to comorbidities as patients age .…”

Efficacy and safety of pegylated full‐length recombinant factor VIII with extended half‐life for perioperative haemostasis in haemophilia A patients

“…(2008) reported a higher median total weight‐adjusted consumption of rFVIII (ADVATE ® ) (910 IU kg −1 ; range: 228–1825) compared to the median consumption of BAX 855 (362 IU kg −1 ; range: 236–863) observed in this study, however, this was presumably due to the relatively high number of orthopaedic surgeries included (21/22), which require increased coagulation factor consumption . A recent study with another commercially available FVIII product in 15 major, mainly orthopaedic surgeries reported a median consumption of 684 (219–1512 IU kg −1 ) . However, comparison of data across studies is difficult due to the different surgery types, duration of rehabilitation, consumption analysis periods and treatment outcome definitions.…”