title: Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.
abstract: BACKGROUND
  The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739).
  
  
  METHODS
  Eligible subjects could enrol in ASPIRE upon completing A-LONG or Kids A-LONG. There were four treatment groups: individualized prophylaxis; weekly prophylaxis; modified prophylaxis (for subjects in whom optimal treatment could not be achieved with individualized or weekly prophylaxis); and episodic treatment. The primary endpoint was development of inhibitors.
  
  
  RESULTS
  A total of 150 A-LONG subjects and 61 Kids A-LONG subjects enrolled in ASPIRE. As of the interim data cut (6 January 2014), the median time on study was 80.9 (A-LONG) and 23.9 (Kids A-LONG) weeks. The majority of subjects (A-LONG, 92.0%; Kids A-LONG, 57.4%) had ≥100 cumulative rFVIIIFc exposure days. No inhibitors were observed. Adverse events were generally consistent with those expected in the general haemophilia A population. Median annualized bleeding rates (ABRs) were low with individualized [A-LONG: 0.66; Kids A-LONG: 0.00 (<6 years old), 1.54 (6 to <12 years old)], weekly (A-LONG: 2.03) and modified (A-LONG: 1.97) prophylaxis. There was no change in prophylactic infusion frequency or total weekly prophylactic dose in the majority of subjects from A-LONG and Kids A-LONG.
  
  
  CONCLUSIONS
  Interim data from ASPIRE confirm the long-term safety of rFVIIIFc and the maintenance of a low ABR with extended-interval prophylactic dosing in patients with severe haemophilia A.
authors.affiliation: Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: B
authors.initials: B
authors.lastname: Nolan
authors.affiliation: University of the Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Mahlangu
authors.affiliation: Addenbrookes Hospital, Cambridge, UK.
authors.forename: D
authors.initials: D
authors.lastname: Perry
authors.affiliation: Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Liesner
authors.affiliation: Puget Sound Blood Center, Seattle, WA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Konkle
authors.affiliation: Basingstoke and North Hampshire Hospital, Basingstoke, UK.
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
authors.affiliation: Lady Cilento Children's Hospital, Brisbane, Qld, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Brown
authors.affiliation: Ogikubo Hospital, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hanabusa
authors.affiliation: Barts and the London Comprehensive Care Center, London, UK.
authors.forename: K J
authors.initials: KJ
authors.lastname: Pasi
authors.affiliation: Medizinsche Universitat Wien, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Pabinger
authors.affiliation: St Paul's Hospital, Vancouver, BC, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Cristiano
authors.affiliation: Biogen, Cambridge, MA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
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
authors.initials: G
authors.lastname: Allen
mesh_terms: D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006467:Hemophilia A / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control / Q000601:surgery; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D008297:Male; D019990:Perioperative Care; D011993:Recombinant Fusion Proteins / Q000009:adverse effects* / Q000627:therapeutic use*; D012449:Safety
chemical_list: D011993:Recombinant Fusion Proteins; D005169:Factor VIII
keywords: factor VIII; haemophilia A; phase 3; prophylaxis; recombinant fusion proteins