T Lissitchkov1, L Rusen2, P Georgiev3, J Windyga4, R Klamroth5, L Gercheva6, L Nemes7, A Tiede8, J Bichler9, S Knaub9, L Belyanskaya9, O Walter9, K J Pasi10. 1. Department of Clinical Haematology in Haemorrhagic Diathesis and Anaemia, Specialized Hospital for Active Treatment "Joan Pavel", Sofia, Bulgaria. 2. Sanador SRL, Bucharest, Romania. 3. Clinic of Haematology, University Multiprofile Hospital for Active Treatment "Sveti Georgi" and Medical University, Plovdiv, Bulgaria. 4. Department of Disorders of Haemostasis and Internal Medicine, Institute of Haematology and Transfusion Medicine, Warsaw, Poland. 5. Department for Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum im Friedrichshain, Berlin, Germany. 6. Clinic of Clinical Haematology, Multiple Hospital for Active Treatment "Sveta Marina", Varna, Bulgaria. 7. Medical Centre, Hungarian Defence Forces, National Haemophilia Centre, Budapest, Hungary. 8. Clinic for Haematology, Haemostaseology, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 9. Octapharma AG, Lachen, Switzerland. 10. The Royal London Hospital, Barts and the London School of Medicine and Dentistry, London, UK.
Abstract
INTRODUCTION: Nuwiq® (human-cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. AIMS/ METHODS: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. RESULTS: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg-1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. CONCLUSION: PK-guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.
INTRODUCTION:Nuwiq® (human-cl rhFVIII) is a 4th generation recombinant humanFVIII, without chemical modification or protein fusion, produced in a human cell-line. AIMS/ METHODS: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. RESULTS: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg-1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. CONCLUSION: PK-guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.
Authors: Samuel Sarmiento Doncel; Gina Alejandra Diaz Mosquera; Javier Mauricio Cortes; Nelson Ramirez Plazas; Francisco Javier Meza; Carol Agudelo Rico Journal: Hematol Rep Date: 2021-11-26
Authors: João A Abrantes; Alexander Solms; Dirk Garmann; Elisabet I Nielsen; Siv Jönsson; Mats O Karlsson Journal: CPT Pharmacometrics Syst Pharmacol Date: 2019-10-30
Authors: Stacy E Croteau; Michael U Callaghan; Joanna Davis; Amy L Dunn; Michael Guerrera; Osman Khan; Ellis J Neufeld; Leslie J Raffini; Michael Recht; Michael Wang; Alfonso Iorio Journal: Res Pract Thromb Haemost Date: 2018-05-27
Authors: Alfonso Iorio; Andrea N Edginton; Victor Blanchette; Jan Blatny; Ana Boban; Marjon Cnossen; Peter Collins; Stacy E Croteau; Katheljin Fischer; Daniel P Hart; Shinya Ito; Joan Korth-Bradley; Stefan Lethagen; David Lillicrap; Mike Makris; Ron Mathôt; Massimo Morfini; Ellis J Neufeld; Jeffrey Spears Journal: Res Pract Thromb Haemost Date: 2018-05-20