Pegylated, full-length, recombinant factor VIII for prophylactic and on-demand treatment of severe hemophilia A

Blood. 2015 Aug 27;126(9):1078-85. doi: 10.1182/blood-2015-03-630897. Epub 2015 Jul 8.


Current management of hemophilia A includes prophylaxis with factor VIII (FVIII) replacement every 2 to 3 days. BAX 855, Baxalta's pegylated full-length recombinant FVIII (rFVIII), was designed to increase half-life and, thus, reduce the frequency of prophylactic infusions while maintaining hemostatic efficacy. BAX 855 was evaluated in previously treated patients with severe hemophilia A who were aged 12 to 65 years. A phase 1 study compared the pharmacokinetic (PK) profile of BAX 855 with that of licensed rFVIII (Advate). In a pivotal study, the annualized bleeding rate (ABR), PK parameters, and efficacy of bleeding treatment were assessed. In the phase 1 study, the mean half-life (T1/2) and the mean residence time of BAX 855 compared with Advate were 1.4- to 1.5-fold higher. These results were confirmed in the pivotal study. The pivotal study met its primary endpoint: Prophylaxis with BAX 855 resulted in an ABR that was significantly lower than half the ABR of on-demand treatment (P < .0001). The median ABR was 1.9, and 39.6% of compliant subjects had no bleeding episodes during prophylaxis, whereas subjects treated on-demand had a median ABR of 41.5. BAX 855 was also efficacious for the treatment of bleeding episodes, with 95.9% of bleeding episodes treated with 1 to 2 infusions and 96.1% having efficacy ratings of excellent/good. No FVIII inhibitory antibodies or safety signals were identified. These studies provide evidence that BAX 855 was safe and efficacious for on-demand treatment and prophylaxis administered twice weekly in patients with hemophilia A. The trials were registered at as #NCT01736475 and #NCT01599819.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Cross-Over Studies
  • Drug Administration Schedule
  • Factor VIII / administration & dosage
  • Factor VIII / chemistry
  • Factor VIII / pharmacokinetics
  • Factor VIII / therapeutic use*
  • Female
  • Hemophilia A / drug therapy*
  • Hemorrhage / prevention & control*
  • Hemostatics / administration & dosage
  • Hemostatics / chemistry
  • Hemostatics / pharmacokinetics
  • Hemostatics / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Polyethylene Glycols / chemistry
  • Prospective Studies
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Young Adult


  • Hemostatics
  • Recombinant Proteins
  • Polyethylene Glycols
  • Factor VIII

Associated data