Guy Young1, Peter W Collins2, Torben Colberg3, Ampaiwan Chuansumrit4, Hideji Hanabusa5, Steven R Lentz6, Johnny Mahlangu7, Evelien P Mauser-Bunschoten8, Claude Négrier9, Johannes Oldenburg10, Turkan Patiroglu11, Elena Santagostino12, Ramin Tehranchi3, Marek Zak3, Faraizah Abdul Karim13. 1. Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA, United States. Electronic address: gyoung@chla.usc.edu. 2. Arthur Bloom Haemophilia Centre, Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, United Kingdom. 3. Novo Nordisk A/S, Søborg, Denmark. 4. Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 5. Department of Hematology, Ogikubo Hospital, Tokyo, Japan. 6. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA, United States. 7. Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, NHLS and University of the Witwatersrand, Johannesburg, South Africa. 8. Van Creveldkliniek, University Medical Centre, Utrecht, The Netherlands. 9. Hôpital Edouard Herriot, University Claude Bernard Lyon 1, Lyon, France. 10. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. 11. Erciyes University Medical Faculty, Kayseri, Turkey. 12. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca' Granda Foundation, Maggiore Hospital Policlinico, Milan, Italy. 13. Haemophilia Center, National Blood Centre, Kuala Lumpur, Malaysia.
Abstract
INTRODUCTION: Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia B patients (FIX activity ≤2%; aged 13-70years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials. METHODS: Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds. RESULTS: Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'. CONCLUSIONS: Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients.
INTRODUCTION: Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia Bpatients (FIX activity ≤2%; aged 13-70years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials. METHODS:Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds. RESULTS: Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'. CONCLUSIONS: Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia Bpatients.
Authors: Junjiang Sun; Baolai Hua; Eric W Livingston; Sarah Taves; Peter B Johansen; Maureane Hoffman; Mirella Ezban; Dougald M Monroe; Ted A Bateman; Paul E Monahan Journal: Blood Date: 2016-12-30 Impact factor: 22.113
Authors: Tim Preijers; Laura Bukkems; Max van Spengler; Frank Leebeek; Marjon Cnossen; Ron Mathôt Journal: Eur J Clin Pharmacol Date: 2021-02-24 Impact factor: 2.953