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DOI: 10.5482/HAMO-15-06-0019
Turoctocog alfa (recombinant factor VIII)
Manufacturing, characteristics and clinical trial resultsTuroctocog alfa (rekombinanter Faktor VIII)Herstellung, Eigenschaften und Ergebnisse klinischer VersucheWriting assistance to the authors during the preparation of this manuscript was provided by Dr. Detlev Janssen, Med-i-Scene Concept GmbH, 91085 Weisendorf, in compliance with international guidelines for good publication practice, and supported by Novo Nordisk Pharma GmbH, 55127 Mainz, Germany.Publication History
received:
15 June 2015
accepted in revised form:
27 July 2015
Publication Date:
28 December 2017 (online)
Summary
Turoctocog alfa (NovoEight®) is a new recombinant factor VIII (rFVIII) with a truncated B domain and a high degree of tyrosine sulphation, similar to plasma-derived FVIII products. The manufacturing process includes double nanofiltration with a 20-nm pore size and immunoaffinity chromatography with monoclonal F25 anti-FVIII antibodies. Treatment with turoctocog alfa can be monitored with both one-stage and chromogenic substrate assays without a product-specific laboratory standard. In total, 213 previouslytreated patients with severe haemophilia A participated in the pivotal part of the clinical trial programme guardianTM. The median annualised bleeding rate during turoctocog alfa prophylaxis was 3.7 and 3.0 in adolescents/adults and children, respectively, with marked differences between participating countries. The success rate for the treatment of breakthrough bleeds was 85% (adults/ adolescents) and 94% (children). A total of 41 surgical procedures (15 major, 26 minor) were performed in 33 patients, with a successful haemostatic response reported in all cases. No patient developed confirmed inhibitors in any of the trials.
Zusammenfassung
Turoctocog alfa (NovoEight®) ist einer neuer rekombinanter Faktor VIII (rFVIII) mit einer verkürzten B-Domäne und einem hohen Grad an Tyrosin-Sulfatierung, ähnlich wie bei plasmatischen FVIII-Produkten. Der Herstellungsprozess umfasst doppelte Nanofiltration (Porengröße 20 nm) und Immunaffinitätschromatographie mit monoklonalen F25-antiFVIII-Antikörpern. Die Behandlung mit Turoctog alfa kann mittels Einstufentest oder chromogenem Substrattest ohne produktspefizische Kalibratoren erfolgen. Am guardianTM Studienprogramm nahmen insgesamt 213 vorbehandelte Patienten mit schwerer Hämophilie A teil. Die mediane Blutungsrate betrug unter Prophylaxe mit Turoctog alfa 3,7 (Erwachsene) bzw. 3,0 (Kinder) Blutungen pro Patient und Jahr, wobei große Unterschiede zwischen den Ländern beobachtet wurden. Die Erfolgsrate in der Behandlung von Durchbruchsblutungen unter Prophylaxe betrug 85% (Erwachsene) bzw. 94 % (Kinder). 41 operative Eingriffe (15 große und 26 kleine) wurden bei 33 Patienten durchgeführt. In allen Fällen war die Substitution hämostyptisch erfolgreich. In keiner der Studien entwickelte ein Patient einen Hemmkörper.
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