title: Recombinant B-domain-deleted porcine sequence factor VIII (r-pFVIII) for the treatment of bleeding in patients with congenital haemophilia A and inhibitors.
abstract: BACKGROUND
  Development of inhibitors to human FVIII (hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A.
  
  
  OBJECTIVE
  This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r-pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors.
  
  
  METHODS
  Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL-1were treated with 50 U kg-1body weight r-pFVIII. Those with pFVIII inhibitor titres of >0.8 BU mL-1received an initial calculated r-pFVIII loading dose followed by 50 U kg-1treatment dose. Treatment continued at 6-hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached.
  
  
  RESULTS
  All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14-34 years) were controlled successfully with eight or fewer injections of r-pFVIII. The median time from bleeding onset to the administration of r-pFVIII was 5.7 h (range: 1.5-20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r-pFVIII (with or without a loading dose, median dose: 200.8 U kg-1; range: 50-576 U kg-1) regardless of pFVIII level. r-pFVIII was well tolerated and no treatment-emergent serious adverse events were considered by the investigator to be related to r-pFVIII administration.
  
  
  CONCLUSIONS
  The results suggest that FVIII replacement therapy with r-pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors.
authors.affiliation: Department of Molecular Medicine and Haematology, Faculty of Health Sciences, Haemophilia Comprehensive Care Centre, NHLS and University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: J N
authors.initials: JN
authors.lastname: Mahlangu
authors.affiliation: City Haemophilia Center, Saint Petersburg, Russia.
authors.forename: T A
authors.initials: TA
authors.lastname: Andreeva
authors.affiliation: Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Macfarlane
authors.affiliation: Mt Sinai School of Medicine, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Key
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D005169:Factor VIII / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D013552:Swine; D055815:Young Adult
chemical_list: D005169:Factor VIII
keywords: factor VIII; factor VIII deficiency; haemophilia A; haemophilia A, congenital; recombinant proteins