title: Long-acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B-LONG study.
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 (R(2) = 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.
authors.affiliation: University of California Davis, Sacramento, CA, USA.
authors.forename: Jerry S
authors.initials: JS
authors.lastname: Powell
authors.forename: Shashikant
authors.initials: S
authors.lastname: Apte
authors.forename: Hervé
authors.initials: H
authors.lastname: Chambost
authors.forename: Cedric
authors.initials: C
authors.lastname: Hermans
authors.forename: Shannon
authors.initials: S
authors.lastname: Jackson
authors.forename: Neil C
authors.initials: NC
authors.lastname: Josephson
authors.forename: Johnny N
authors.initials: JN
authors.lastname: Mahlangu
authors.forename: Margareth C
authors.initials: MC
authors.lastname: Ozelo
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peerlinck
authors.forename: John
authors.initials: J
authors.lastname: Pasi
authors.forename: David
authors.initials: D
authors.lastname: Perry
authors.forename: Margaret V
authors.initials: MV
authors.lastname: Ragni
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jiang
authors.forename: Shuanglian
authors.initials: S
authors.lastname: Li
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Cristiano
authors.forename: Alison
authors.initials: A
authors.lastname: Innes
authors.forename: Karen
authors.initials: K
authors.lastname: Nugent
authors.forename: Aoife
authors.initials: A
authors.lastname: Brennan
authors.forename: Alvin
authors.initials: A
authors.lastname: Luk
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Allen
authors.forename: Glenn F
authors.initials: GF
authors.lastname: Pierce
authors.forename: Brian
authors.initials: B
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000328:Adult; D001780:Blood Coagulation Tests; D018890:Chemoprevention; D019468:Disease Management; D005164:Factor IX / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002836:Hemophilia B / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006488:Hemostasis, Surgical; D006801:Humans; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011993:Recombinant Fusion Proteins; D005164:Factor IX
keywords: clinical trial, phase 3; factor IX; haemophilia B; pharmacokinetics; surgery