Long-acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B-LONG study

Jerry S Powell, Shashikant Apte, Hervé Chambost, Cedric Hermans, Shannon Jackson, Neil C. Josephson, Johnny N. Mahlangu, Margareth C. Ozelo, Kathelijne Peerlinck, John Pasi, David Perry, Margaret V. Ragni, Xuefeng Wang, Haiyan Jiang, Shuanglian Li, Lynda M. Cristiano, Alison Innes, Karen Nugent, Aoife Brennan, Alvin LukGeoffrey Allen, Glenn F. Pierce, Brian Robinson

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

In 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 (85·7%), 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 (R2 = 0·9586, P < 0·001) 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.

Original languageEnglish (US)
Pages (from-to)124-134
Number of pages11
JournalBritish Journal of Haematology
Volume168
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • Clinical trial, phase 3
  • Factor ix
  • Haemophilia b
  • Pharmacokinetics
  • Surgery

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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    Powell, J. S., Apte, S., Chambost, H., Hermans, C., Jackson, S., Josephson, N. C., Mahlangu, J. N., Ozelo, M. C., Peerlinck, K., Pasi, J., Perry, D., Ragni, M. V., Wang, X., Jiang, H., Li, S., Cristiano, L. M., Innes, A., Nugent, K., Brennan, A., ... Robinson, B. (2015). Long-acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B-LONG study. British Journal of Haematology, 168(1), 124-134. https://doi.org/10.1111/bjh.13112