title: Novel, human cell line-derived recombinant factor VIII (Human-cl rhFVIII, Nuwiq®) in children with severe haemophilia A: efficacy, safety and pharmacokinetics.
abstract: BACKGROUND
  Nuwiq®(Human-cl rhFVIII) is a new-generation recombinant factor VIII (rFVIII) protein, without chemical modification or fusion to any other protein, produced in a human cell line.
  
  
  OBJECTIVE
  This prospective, open-label, multinational phase III study assessed the efficacy and safety of Human-cl rhFVIII in 59 previously treated patients (PTPs) with severe haemophilia A aged 2-12 years (2-5 [N = 29]; 6-12 [N = 30]) during standard prophylaxis (≥50 exposure days and ≥6 months). Efficacy in treating breakthrough bleeds and during surgical prophylaxis was also assessed.
  
  
  RESULTS
  An initial pharmacokinetic assessment (N = 13 per age subgroup) demonstrated comparable results with the one-stage and chromogenic assays. Mean (SD) half-life was 11.9 (5.4) and 13.1 (2.6) hours in children aged 2-5 years and 6-12 years respectively (one-stage assay). Prophylactic efficacy, based on mean monthly bleeding rate, was 'excellent' or 'good' in 91.5% of children for all bleeds and in 96.6% of children for spontaneous bleeds. Mean (SD) annualized bleeding rate was 4.12 (5.22) [median 1.9] for all bleeds, 1.50 (3.32) [median 0] for spontaneous bleeds and 2.34 (3.54) [median 1.57] for traumatic bleeds. There were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in the treatment of 82.4% of breakthrough bleeds. Overall efficacy during five major surgeries was rated as 'excellent'. There were no FVIII inhibitors or treatment-related serious adverse events.
  
  
  CONCLUSIONS
  These results in paediatric PTPs indicate that Human-cl rhFVIII is effective for the prevention and treatment of bleeds.
authors.affiliation: Department of Pediatrics, Hematology and Oncology, Warsaw Medical University, Warsaw, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Klukowska
authors.affiliation: Department of Paediatric Haematology and Oncology, Zabrze, Medical University of Silesia, Katowice, Poland.
authors.forename: T
authors.identifier: http://orcid.org/0000-0001-5336-261X
authors.initials: T
authors.lastname: Szczepański
authors.affiliation: Moscow Children's Hematology Centre, Moscow, Russia.
authors.forename: V
authors.initials: V
authors.lastname: Vdovin
authors.affiliation: Octapharma AG, Lachen, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Knaub
authors.affiliation: Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.affiliation: Great Ormond Street Hospital for Children, NHS Trust Haemophilia Centre, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Liesner
keywords: Human-cl rhFVIII; Nuwiq; efficacy; haemophilia A; immunogenicity; safety