Premium
Long‐acting recombinant factor IX Fc fusion protein ( rFIXF c) for perioperative management of subjects with haemophilia B in the phase 3 B‐LONG study
Author(s) -
Powell Jerry S.,
Apte Shashikant,
Chambost Hervé,
Hermans Cedric,
Jackson Shan,
Josephson Neil C.,
Mahlangu Johnny N.,
Ozelo Margareth C.,
Peerlinck Kathelijne,
Pasi John,
Perry David,
Ragni Margaret V.,
Wang Xuefeng,
Jiang Haiyan,
Li Shuanglian,
Cristiano Lynda M.,
Innes Alison,
Nugent Karen,
Brennan Aoife,
Luk Alvin,
Allen Geoffrey,
Pierce Glenn F.,
Robinson Brian
Publication year - 2015
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.13112
Subject(s) - medicine , haemophilia b , haemophilia , perioperative , dosing , factor ix , pharmacokinetics , population , surgery , haemophilia a , anesthesia , environmental health
Summary In the phase 3 B‐LONG (Recombinant Factor IX Fc Fusion Protein [ rFIXF c] 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, rFIXF c 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 rFIXF c was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXF c 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 rFIXF c infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation ( R 2 = 0·9586, P < 0·001) between observed and population pharmacokinetic model‐predicted FIX activity suggests surgery did not impact rFIXF c pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXF c was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXF c pharmacokinetics.