Long-term safety and efficacy of extended-interval prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) in subjects with haemophilia B

K John Pasi, Kathelijn Fischer, Margaret Ragni, Beatrice Nolan, David J Perry, Roshni Kulkarni, Margareth Ozelo, Johnny Mahlangu, Amy D Shapiro, Ross I Baker, Carolyn M Bennett, Christopher Barnes, Johannes Oldenburg, Tadashi Matsushita, Huixing Yuan, Alejandra Ramirez-Santiago, Glenn F Pierce, Geoffrey Allen, Baisong Mei

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The safety, efficacy, and prolonged half-life of recombinant factor IX Fc fusion protein (rFIXFc) were demonstrated in the Phase 3 B-LONG (adults/adolescents ≥12 years) and Kids B-LONG (children <12 years) studies of subjects with haemophilia B (≤2 IU/dl). Here, we report interim, long-term safety and efficacy data from B-YOND, the rFIXFc extension study. Eligible subjects who completed B-LONG or Kids B-LONG could enrol in B-YOND. There were four treatment groups: weekly prophylaxis (20-100 IU/kg every 7 days), individualised prophylaxis (100 IU/kg every 8-16 days), modified prophylaxis (further dosing personalisation to optimise prophylaxis), and episodic (on-demand) treatment. Subjects could change treatment groups at any point. Primary endpoint was inhibitor development. One hundred sixteen subjects enrolled in B-YOND. From the start of the parent studies to the B-YOND interim data cut, median duration of rFIXFc treatment was 39.5 months and 21.9 months among adults/adolescents and children, respectively; 68/93 (73.1 %) adults/adolescents and 9/23 (39.1 %) children had ≥100 cumulative rFIXFc exposure days. No inhibitors were observed. Median annualised bleeding rates (ABRs) were low in all prophylaxis regimens: weekly (≥12 years: 2.3; <6 years: 0.0; 6 to <12 years: 2.7), individualised (≥12 years: 2.3; 6 to <12 years: 2.4), and modified (≥12 years: 2.4). One or two infusions were sufficient to control 97 % (adults/adolescents) and 95 % (children) of bleeding episodes. Interim data from B-YOND are consistent with data from B-LONG and Kids B-LONG, and confirm the long-term safety of rFIXFc, absence of inhibitors, and maintenance of low ABRs with prophylactic dosing every 1-2 weeks.

Original languageEnglish
Pages (from-to)508-518
Number of pages11
JournalThrombosis and Haemostasis
Volume117
Issue number3
DOIs
Publication statusPublished - Mar 2017

Keywords

  • Factor IX
  • Haemophilia
  • Prophylaxis
  • Recombinant fusion proteins
  • Hemophilia B/blood
  • Drug Administration Schedule
  • Hemorrhage/blood
  • Humans
  • Middle Aged
  • Risk Factors
  • Coagulants/administration & dosage
  • Male
  • Treatment Outcome
  • Factor IX/administration & dosage
  • Antibodies, Neutralizing/blood
  • Recombinant Fusion Proteins/administration & dosage
  • Young Adult
  • Hemostasis/drug effects
  • Immunoglobulin Fc Fragments/administration & dosage
  • Time Factors
  • Adolescent
  • Adult
  • Child
  • prophylaxis
  • haemophilia
  • recombinant fusion proteins

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