Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery

C. Négrier, F. Abdul Karim, L. M. Lepatan, A. Lienhart, M. F. López-Fernández, J. Mahlangu, I. Pabinger, Y. Li, D. Wolko, C. Voigt, I. Jacobs, E. Santagostino

Research output: Contribution to journalArticle

Abstract

Introduction: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment. Aim: To determine the efficacy and safety of rIX-FP in the perioperative setting. Methods: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required. Results: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6–12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg−1 preoperatively and 375 IU kg−1 overall. No subject developed inhibitors to FIX or antibodies to rIX-FP. Conclusion: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.

Original languageEnglish
Pages (from-to)e259-e266
JournalHaemophilia
Volume22
Issue number4
DOIs
Publication statusPublished - Jul 1 2016

Keywords

  • albumin fusion proteins
  • factor IX
  • haemophilia B
  • orthopaedic surgery
  • recombinant fusion proteins

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

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    Négrier, C., Abdul Karim, F., Lepatan, L. M., Lienhart, A., López-Fernández, M. F., Mahlangu, J., Pabinger, I., Li, Y., Wolko, D., Voigt, C., Jacobs, I., & Santagostino, E. (2016). Efficacy and safety of long-acting recombinant fusion protein linking factor IX with albumin in haemophilia B patients undergoing surgery. Haemophilia, 22(4), e259-e266. https://doi.org/10.1111/hae.12972