title: Treatment of bleeding episodes with recombinant factor VIII Fc fusion protein in A-LONG study subjects with severe haemophilia A.
abstract: BACKGROUND
  The Phase 3 A-LONG study demonstrated the safety and efficacy of rFVIIIFc for the control and prevention of bleeding episodes in severe haemophilia A.
  
  
  OBJECTIVE
  To describe the treatment of bleeding episodes with rFVIIIFc in the A-LONG study.
  
  
  METHODS
  A-LONG subjects (<1 IU dL-1endogenous FVIII) were treated with individualized prophylaxis (Arm 1), weekly prophylaxis (Arm 2) or episodic treatment (Arm 3). Information recorded for each bleeding episode included type, location and dose to treat the episode.
  
  
  RESULTS
  During A-LONG, 757 bleeding episodes occurred during the efficacy period; the majority [456 (60%)] occurred in Arm 3 (episodic treatment). Of 93 subjects in the prophylaxis arms who entered the study with target joints, 43 (60%) in Arm 1 and 11 (52%) in Arm 2 did not experience a target joint bleed. Overall, 98% of bleeding episodes (and 98% of bleeds involving a target joint) resolved with one or two infusions; the median dose per infusion to treat a bleed was 27 IU kg-1(27 IU kg-1for target joints). Using population pharmacokinetic simulations, FVIII activity levels were predicted to be below the upper limit of normal (150 IU dL-1) in most patients in the event that rFVIIIFc is used to treat a bleeding episode in close proximity to a prophylactic dose.
  
  
  CONCLUSIONS
  These findings demonstrate the efficacy of rFVIIIFc for the treatment of acute bleeding episodes in subjects with severe haemophilia A, regardless of treatment regimen.
authors.affiliation: Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Shapiro
authors.affiliation: Faculty of Health Sciences, University of the Witwatersrand and NHLS Hospital, Parktown, Johannesburg, South Africa.
authors.forename: J N
authors.initials: JN
authors.lastname: Mahlangu
authors.affiliation: Addenbrookes Hospital, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Perry
authors.affiliation: Barts and The London Comprehensive Care Center, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Pasi
authors.affiliation: Orthopaedic Hemophilia Treatment Center, Los Angeles, CA, USA.
authors.forename: D V
authors.initials: DV
authors.lastname: Quon
authors.affiliation: Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Chowdary
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Tsao
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Innes
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: G F
authors.initials: GF
authors.lastname: Pierce
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Allen
mesh_terms: D005169:Factor VIII / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000150:complications* / Q000517:prevention & control; D006470:Hemorrhage / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics*; D008297:Male; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012449:Safety; D016896:Treatment Outcome
chemical_list: D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D005169:Factor VIII
keywords: bleeding; factor VIII; haemophilia A; phase 3; prophylaxis; recombinant Fc fusion protein