title: Extended half-life pegylated, full-length recombinant factor VIII for prophylaxis in children with severe haemophilia A.
abstract: BACKGROUND
  Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T1/2) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy.
  
  
  OBJECTIVE
  To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A.
  
  
  METHODS
  PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg-1BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg-1were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg-1.
  
  
  RESULTS
  T1/2and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg-1of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred.
  
  
  CONCLUSIONS
  Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.
authors.affiliation: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
authors.forename: E S
authors.initials: ES
authors.lastname: Mullins
authors.affiliation: SI Institute of Blood Pathology and Transfusion Medicine of NAMSU, Lviv, Ukraine.
authors.forename: O
authors.initials: O
authors.lastname: Stasyshyn
authors.affiliation: Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M T
authors.initials: MT
authors.lastname: Alvarez-Román
authors.affiliation: Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia.
authors.forename: D
authors.initials: D
authors.lastname: Osman
authors.affiliation: Great Ormond Street Hospital for Children, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Liesner
authors.affiliation: Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
authors.forename: W
authors.initials: W
authors.lastname: Engl
authors.affiliation: Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Sharkhawy
authors.affiliation: Baxalta Innovations GmbH, now part of Shire, Vienna, Austria.
authors.forename: B E
authors.initials: BE
authors.lastname: Abbuehl
mesh_terms: D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011788:Quality of Life
chemical_list: C427184:recombinant factor VIII SQ; D005169:Factor VIII
keywords: children; extended half-life FVIII; prophylaxis