Safety and efficacy of a glycoPEGylated rFVIII (turoctocog alpha pegol, N8-GP) in paediatric patients with severe haemophilia A

Thromb Haemost. 2017 Aug 30;117(9):1705-1713. doi: 10.1160/TH17-03-0166. Epub 2017 Jul 6.


Turoctocog alfa pegol (N8-GP, Novo Nordisk, Bagsværd, Denmark), an extended half-life glycoPEGylated recombinant factor VIII (rFVIII), is being developed for prophylaxis and treatment of bleeds in haemophilia A patients. pathfinder™5 is a multinational, open-label, single-arm trial to assess safety, efficacy and pharmacokinetics of N8-GP in paediatric (<12 years), previously treated patients. Boys with severe haemophilia A (<1 % FVIII), no history of inhibitors and previously treated with FVIII products (>50 exposure days [ED] for patients aged 0-5 years [younger cohort]; >150 ED for patients aged 6-11 years [older cohort]) were included. For prophylaxis, N8-GP was dosed at 50-75 IU/kg twice weekly; bleeds were treated with 20-75 IU/kg. Half-life was estimated for the patients' previous FVIII product and for N8-GP. Sixty-eight patients received N8-GP; none developed inhibitors and no other concerns were identified. Median annualised bleeding rate was 1.95 (1.94 and 1.97 in the younger and older cohorts, respectively). Twenty-nine patients (42.6 %; 15 younger and 14 older children, respectively) did not report any bleeding while on N8-GP prophylaxis; 39 patients (57.4 %; 19 younger and 20 older children, respectively) reported 70 bleeds (all mild/moderate). N8-GP treatment was successful for 78.6 % of bleeds in all patients, 80.0 % in younger and 77.5 % in older patients. Most bleeds (80.0 %) were treated with ≤2 injections. Half-life ratio between N8-GP and the patients' previous FVIII product was 1.85. N8-GP was well tolerated and provided effective prophylaxis and treatment of bleeds in paediatric patients with severe haemophilia A.

Keywords: GlycoPEGylated; haemophilia A; paediatrics; phase III; recombinant FVIII.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asia
  • Child
  • Child, Preschool
  • Coagulants / adverse effects
  • Coagulants / pharmacokinetics
  • Coagulants / therapeutic use*
  • Europe
  • Factor VIII / adverse effects
  • Factor VIII / pharmacokinetics
  • Factor VIII / therapeutic use*
  • Half-Life
  • Hemarthrosis / blood
  • Hemarthrosis / diagnosis
  • Hemarthrosis / prevention & control*
  • Hemophilia A / blood
  • Hemophilia A / diagnosis
  • Hemophilia A / drug therapy*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • North America
  • Patient Safety
  • Risk Assessment
  • Severity of Illness Index
  • Treatment Outcome


  • Coagulants
  • recombinant factor VIII N8
  • Factor VIII