title: Clinical evaluation of glycoPEGylated recombinant FVIII: Efficacy and safety in severe haemophilia A.
abstract: Turoctocog alfa pegol (N8-GP) is a novel glycoPEGylated extended half-life recombinant factor VIII (FVIII) product developed for prophylaxis and treatment of bleeds in patients with haemophilia A, to enable higher activity levels with less frequent injections compared with standard FVIII products. This phase III (NCT01480180), multinational, open-label, non-randomised trial evaluated the safety and clinical efficacy of N8-GP when administered for treatment of bleeds and for prophylaxis, in previously treated patients aged ≥12 years with severe haemophilia A. Patients were allocated to receive N8-GP for prophylaxis or on-demand treatment for up to 1.8 years. Patients on prophylaxis were administered one dose of 50 IU/kg of N8-GP every fourth day. Bleeds were treated with doses of 20-75 IU/kg. Total exposure to N8-GP in the trial was 14,114 exposure days (159 patient-years). For the prophylaxis arm (n=175), the median annualised bleeding rate (ABR) was 1.33 (interquartile range, 0.00-4.61), the mean ABR was 3.70 (95 % confidence interval 2.94-4.66) and 70 (40 %) patients had no bleeds during the trial. Across treatment arms, 83.6 % of bleeds resolved with one injection and 95.5 % with up to two injections. N8-GP had a favourable safety profile and was well tolerated. The frequency and types of adverse events reported were as expected in this population. One patient developed inhibitory antibodies against FVIII (≥0.6 Bethesda units [BU]) after 93 N8-GP exposure days. No clinically significant safety concerns were identified and N8-GP was effective for prophylaxis and treatment of bleeds in previously treated patients.
authors.affiliation: Paul Giangrande, Oxford Haemophilia & Thrombosis Centre, Churchill Hospital, Headington, Oxford OX3 7LE, UK, Tel.: +44 1865 225300, Fax: +44 1865 225608, E-mail: paul.giangrande@ndm.ox.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Giangrande
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreeva
authors.forename: Pratima
authors.initials: P
authors.lastname: Chowdary
authors.forename: Silke
authors.initials: S
authors.lastname: Ehrenforth
authors.forename: Hideji
authors.initials: H
authors.lastname: Hanabusa
authors.forename: Frank W G
authors.initials: FW
authors.lastname: Leebeek
authors.forename: Steven R
authors.initials: SR
authors.lastname: Lentz
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nemes
authors.forename: Lone Hvitfeldt
authors.initials: LH
authors.lastname: Poulsen
authors.forename: Elena
authors.initials: E
authors.lastname: Santagostino
authors.forename: Chur Woo
authors.initials: CW
authors.lastname: You
authors.forename: Wan Hui Ong
authors.initials: WH
authors.lastname: Clausen
authors.forename: Peter G
authors.initials: PG
authors.lastname: Jönsson
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006470:Hemorrhage / Q000097:blood / Q000517:prevention & control*; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; C577506:recombinant factor VIII N8; D005169:Factor VIII
keywords: GlycoPEGylated; efficacy; haemostasis; recombinant factor VIII; safety