R J Liesner1, M Abashidze2, O Aleinikova3, C Altisent4, M J Belletrutti5, A Borel-Derlon6, M Carcao7, H Chambost8, A K C Chan9, L Dubey10, J Ducore11, N A Fouzia12, M Gattens13, Y Gruel14, B Guillet15, N Kavardakova16, M El Khorassani17, A Klukowska18, T Lambert19, S Lohade20, M Sigaud21, V Turea22, J K M Wu23, V Vdovin24, A Pavlova25, M Jansen26, L Belyanskaya27, O Walter27, S Knaub27, E J Neufeld28. 1. Great Ormond Hospital for Children NHS Trust Haemophilia Centre, London, UK. 2. JSC Institute of Haematology and Transfusiology, Tbilisi, Georgia. 3. Republican Scientific and Practical Centre of Children Oncology, Hematology and Immunology, Minsk, Belarus. 4. Unitat d'Hemofilia, Hospital Vall D'Hebron, Barcelona, Spain. 5. Pediatric Hematology, Department of Pediatrics, University of Alberta, Edmonton, AB, Canada. 6. Hôpital de la Côte de Nacre, Caen, France. 7. Hospital for Sick Children, Toronto, ON, Canada. 8. Department of Pediatric Hematology Oncology, Children Hospital La Timone, APHM and Inserm, UMR 1062, Aix Marseille University, Marseille, France. 9. Division of Pediatric Hematology/Oncology, McMaster University, Hamilton, ON, Canada. 10. Western Ukrainian Specialized Children's Medical Centre, Lviv, Ukraine. 11. Department of Pediatrics, UC Davis Medical Center, Sacramento, CA, USA. 12. Christian Medical College Vellore, Vellore, India. 13. Cambridge University Hospital NHS Foundation Trust, Cambridge, UK. 14. Hôpital Trousseau, Centre Régional de Traitement de l'Hémophilie, Tours, France. 15. Haemophilia Treatment Centre of Rennes-Brittany, University Hospital of Rennes, Rennes, France. 16. National Children's Specialized Clinic "OHMATDET", Kiev, Ukraine. 17. Centre de traitement de l'hémophilie, University Mohamed V, Rabat, Morocco. 18. Warsaw Medical University, Warsaw, Poland. 19. CRTH Hôpital Universitaire Bicêtre APHP, Le Kremlin Bicêtre, France. 20. Sahyadri Speciality Hospital, Pune, India. 21. Centre Régional de Traitement de I'Hémophilie, University Hospital of Nantes, Nantes, France. 22. Scientific Research Institute of Mother and Child Health Care, Chişinău, Moldova. 23. B.C. Children's Hospital, Vancouver, BC, Canada. 24. Morozovskaya Children's Hospital, Moscow, Russia. 25. Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. 26. Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria. 27. Octapharma AG, Lachen, Switzerland. 28. St. Jude Children's Research Hospital, Memphis, TN, USA.
Abstract
INTRODUCTION: Nuwiq® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. METHODS: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. RESULTS: Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. CONCLUSION: These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq® .
INTRODUCTION:Nuwiq® (Human-cl rhFVIII) is a fourth generation recombinant FVIII, produced in a human cell line, without chemical modification or protein fusion. No inhibitors developed in studies with Nuwiq® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. METHODS: The study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5 years maximum. The primary objective is to assess the immunogenicity of Nuwiq® (inhibitor activity ≥0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. RESULTS: Data for 66 PUPs with ≥20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24). Five patients developed low-titre inhibitors (4 transient). The cumulative incidence (95% confidence interval) was 12.8% (4.5%, 21.2%) for HT inhibitors and 20.8% (10.7%, 31.0%) for all inhibitors. During inhibitor-free periods, median annualized bleeding rates during prophylaxis were 0 for spontaneous bleeds and 2.40 for all bleeds. Efficacy was rated as "excellent" or "good" in treating 91.8% of bleeds. Efficacy of surgical prophylaxis was "excellent" or "good" for 8 (89%) procedures and "moderate" for 1 (11%). No tolerability concerns were evident. CONCLUSION: These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq® .
Authors: Ri J Liesner; Aby Abraham; Carmen Altisent; Mark J Belletrutti; Manuel Carcao; Manuela Carvalho; Hervé Chambost; Anthony K C Chan; Leonid Dubey; Jonathan Ducore; Michael Gattens; Paolo Gresele; Yves Gruel; Benoit Guillet; Victor Jimenez-Yuste; Lidija Kitanovski; Anna Klukowska; Sunil Lohade; Maria Elisa Mancuso; Johannes Oldenburg; Anna Pavlova; Berardino Pollio; Marianne Sigaud; Vladimir Vdovin; Kateryna Vilchevska; John K M Wu; Martina Jansen; Larisa Belyanskaya; Olaf Walter; Sigurd Knaub; Ellis J Neufeld Journal: Thromb Haemost Date: 2021-02-13 Impact factor: 5.249