title: Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial.
abstract: This multinational, randomized, single-blind trial investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously treated patients with hemophilia B (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to either 10 IU/kg or 40 IU/kg once weekly or to on-demand treatment of 28 weeks. No patients developed inhibitors, and no safety concerns were identified. Three hundred forty-five bleeding episodes were treated, with an estimated success rate of 92.2%. The median annualized bleeding rates (ABRs) were 1.04 in the 40 IU/kg prophylaxis group, 2.93 in the 10 IU/kg prophylaxis group, and 15.58 in the on-demand treatment group. In the 40 IU/kg group, 10 (66.7%) of 15 patients experienced no bleeding episodes into target joints compared with 1 (7.7%) of 13 patients in the 10 IU/kg group. Health-related quality of life (HR-QoL) assessed with the EuroQoL-5 Dimensions visual analog scale score improved from a median of 75 to 90 in the 40 IU/kg prophylaxis group. Nonacog beta pegol was well tolerated and efficacious for the treatment of bleeding episodes and was associated with low ABRs in patients receiving prophylaxis. Once-weekly prophylaxis with 40 IU/kg resolved target joint bleeds in 66.7% of the affected patients and improved HR-QoL. This trial was registered at www.clinicaltrials.gov as #NCT01333111.
authors.affiliation: Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom;
authors.forename: Peter W
authors.initials: PW
authors.lastname: Collins
authors.affiliation: Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA;
authors.forename: Guy
authors.initials: G
authors.lastname: Young
authors.affiliation: Haemophilia R&D Portfolio, Novo Nordisk A/S, Soeborg, Denmark;
authors.forename: Karin
authors.initials: K
authors.lastname: Knobe
authors.affiliation: Haemophilia Centre, National Blood Centre, Kuala Lumpur, Malaysia;
authors.forename: Faraizah Abdul
authors.initials: FA
authors.lastname: Karim
authors.affiliation: Division of Hematology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;
authors.forename: Pantep
authors.initials: P
authors.lastname: Angchaisuksiri
authors.affiliation: Haemophilia Clinical Operations, Novo Nordisk A/S, Soeborg, Denmark;
authors.forename: Claus
authors.initials: C
authors.lastname: Banner
authors.affiliation: Gazi University Medical School, Ankara, Turkey;
authors.forename: Türkiz
authors.initials: T
authors.lastname: Gürsel
authors.affiliation: Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, National Health Laboratory Services and University of the Witwatersrand, Johannesburg, South Africa;
authors.forename: Johnny
authors.initials: J
authors.lastname: Mahlangu
authors.affiliation: Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan;
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Van Creveldkliniek, University Medical Centre, Utrecht, The Netherlands;
authors.forename: Eveline P
authors.initials: EP
authors.lastname: Mauser-Bunschoten
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany;
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.affiliation: Division of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, NY; and.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Walsh
authors.affiliation: Hôpital Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France.
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005164:Factor IX / Q000008:administration & dosage*; D006207:Half-Life; D002836:Hemophilia B / Q000188:drug therapy*; D006470:Hemorrhage; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011788:Quality of Life; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012044:Regression Analysis; D016037:Single-Blind Method; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; C000592276:nonacog beta pegol; D011092:Polyethylene Glycols; D005164:Factor IX