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

Thromb Haemost. 2017 Feb 28;117(3):508-518. doi: 10.1160/TH16-05-0398. Epub 2016 Dec 22.

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 to 2 weeks.

Keywords: Factor IX; haemophilia; prophylaxis; recombinant fusion proteins.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / blood
  • Child
  • Coagulants / administration & dosage*
  • Coagulants / adverse effects
  • Drug Administration Schedule
  • Factor IX / administration & dosage*
  • Factor IX / adverse effects
  • Factor IX / immunology
  • Hemophilia B / blood
  • Hemophilia B / diagnosis
  • Hemophilia B / drug therapy*
  • Hemorrhage / blood
  • Hemorrhage / prevention & control*
  • Hemostasis / drug effects*
  • Humans
  • Immunoglobulin Fc Fragments / administration & dosage*
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / immunology
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / immunology
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • Coagulants
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • factor IX Fc fusion protein
  • Factor IX