Johannes Oldenburg1, Manuel Carcao2, Steven R Lentz3, Johnny Mahlangu4, Maria Elisa Mancuso5, Tadashi Matsushita6, Claude Négrier7, Wan Hui Ong Clausen8, Silke Ehrenforth8, Guy Young9. 1. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. 2. Division of Haematology/Oncology, Department of Paediatrics and Research Institute, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 3. Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa. 4. Haemophilia Comprehensive Care Centre, Faculty of Health Sciences, NHLS and University of the Witwatersrand, Johannesburg, South Africa. 5. Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 6. Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan. 7. Haemophilia and Thrombosis Centre, Louis Pradel Hospital, University Claude Bernard, Lyon, France. 8. Novo Nordisk A/S, Søborg, Denmark. 9. Hemostasis and Thrombosis Center, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, California.
Abstract
INTRODUCTION: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. AIM: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on-but not limited to-prophylaxis at 40 IU/kg. METHODS: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. RESULTS: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults. CONCLUSION: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.
INTRODUCTION: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia Bpatients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products. AIM: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on-but not limited to-prophylaxis at 40 IU/kg. METHODS: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing. RESULTS: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults. CONCLUSION: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia Bpatients.
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
Authors: Davide Matino; Alfonso Iorio; Arun Keepanasseril; Federico Germini; Alexandre Caillaud; Manuel Carcao; Julia Hews-Girard; Emma Iserman; Paula James; Adrienne Lee; Chai W Phua; Haowei Linda Sun; Jerome Teitel; Man-Chiu Poon Journal: Res Pract Thromb Haemost Date: 2022-03-31
Authors: Tim Preijers; Lisette M Schütte; Marieke J H A Kruip; Marjon H Cnossen; Frank W G Leebeek; Reinier M van Hest; Ron A A Mathôt Journal: Clin Pharmacokinet Date: 2021-01 Impact factor: 6.447