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CC BY 4.0 · Thromb Haemost 2021; 121(11): 1400-1408
DOI: 10.1055/s-0040-1722623
Coagulation and Fibrinolysis

Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study

Authors

  • Ri J. Liesner

    1   Great Ormond Street Hospital for Children NHS Trust Haemophilia Centre, NIHR GOSH BRC, London, United Kingdom

  • Aby Abraham

    2   Department of Hematology, Christian Medical College, Vellore, India

  • Carmen Altisent

    3   Unitat d'Hemofilia, Hospital Vall D'Hebron, Barcelona, Spain

  • Mark J. Belletrutti

    4   Pediatric Hematology, Department of Pediatrics, University of Alberta, Edmonton, Canada

  • Manuel Carcao

    5   Division of Haematology/Oncology and Child Health Evaluative Sciences, Department of Paediatrics, Research Institute, Hospital for Sick Children, Toronto, Canada

  • Manuela Carvalho

    6   Congenital Coagulopathies Reference Centre, São João University Hospital Centre, Porto, Portugal

  • Hervé Chambost

    7   AP-HM, Department of Pediatric Hematology Oncology, Children Hospital La Timone, Aix Marseille Univ, INSERM, INRA, C2VN, Marseille, France

  • Anthony K. C. Chan

    8   Division of Pediatric Hematology/Oncology, McMaster University, Hamilton, Canada

  • Leonid Dubey

    9   Department of Pediatrics, Western Ukrainian Specialized Children's Medical Centre, Lviv, Ukraine

  • Jonathan Ducore

    10   Department of Pediatrics, University of California Davis Medical Center, Sacramento, United States

  • Michael Gattens

    11   Department of Paediatric Haematology and Oncology, Addenbrooke’s Hospital, Cambridge University Hospital NHS Foundation Trust, Cambridge, United Kingdom

  • Paolo Gresele

    12   Department of Medicine and Surgery, University of Perugia, Perugia, Italy

  • Yves Gruel

    13   Centre Régional de Traitement de l'Hémophilie, Hôpital Trousseau, Tours, France

  • Benoit Guillet

    14   Haemophilia Treatment Centre, Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085, Rennes, France

  • Victor Jimenez-Yuste

    15   Servicio de Hematología, Hospital Univeristario La Paz, Autónoma University, Madrid, Spain

  • Lidija Kitanovski

    16   Department of Haemato-Oncology, University Medical Center Ljubljana, Ljubljana, Slovenia

  • Anna Klukowska

    17   Department of Pediatrics, Haematology and Oncology, Warsaw Medical University, Warsaw, Poland

  • Sunil Lohade

    18   Department of Hematology, Sahyadri Speciality Hospital, Pune, India

  • Maria Elisa Mancuso

    19   Center for Thrombosis and Hemorrhagic Diseases, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy

  • Johannes Oldenburg

    20   Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

  • Anna Pavlova

    20   Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany

  • Berardino Pollio

    21   Department of Transfusion Medicine, Regina Margherita Children Hospital of Turin, Turin, Italy

  • Marianne Sigaud

    22   Centre Régional de Traitement de I'Hémophilie, University Hospital of Nantes, Nantes, France

  • Vladimir Vdovin

    23   Department of Hematology, Morozovskaya Children's Hospital, Moscow, Russian Federation

  • Kateryna Vilchevska

    24   Department of Hematology, State Institution “Institute of Urgent and Reconstructive Surgery named after V.K. Gusak of National Academy of Medical Sciences of Ukraine,” Donetsk, Ukraine

  • John K. M. Wu

    25   British Columbia Children's Hospital, Vancouver, Canada

  • Martina Jansen

    26   Octapharma Pharmazeutika Produktionsges.mbH, Vienna, Austria

  • Larisa Belyanskaya

    27   Octapharma AG, Lachen, Switzerland

  • Olaf Walter

    27   Octapharma AG, Lachen, Switzerland

  • Sigurd Knaub

    27   Octapharma AG, Lachen, Switzerland

  • Ellis J. Neufeld

    28   St. Jude Children's Research Hospital, Memphis, Tennessee, United States

Funding This trial was sponsored by Octapharma AG (Lachen, Switzerland) with medical writing assistance provided by nspm ltd, Meggen, Switzerland, and funded by Octapharma AG.
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Abstract

Introduction FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

Methods The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs. NuProtect was a prospective, multinational, open-label, non-controlled, phase III study. PUPs with severe haemophilia A (FVIII:C <1%) of any age and ethnicity were treated with simoctocog alfa for 100 exposure days or a maximum of 5 years. Patients were true PUPs without prior exposure to FVIII concentrates or blood components. Inhibitor titres were measured with the Nijmegen-modified Bethesda assay; cut-off for positivity was 0.6 BU mL−1 (≥0.6 to <5 low-titre, ≥5 high titre).

Results A total of 108 PUPs with a median age at first treatment of 12.0 months (interquartile range: 8.0–23.5) were treated with simoctocog alfa. F8 mutation type was known for 102 patients (94.4%) of whom 90 (88.2%) had null F8 mutations and 12 (11.8%) had non-null mutations. Of 105 PUPs evaluable for inhibitor development, 28 (26.7%) developed inhibitors; 17 high titre (16.2%) and 11 low titre (10.5%). No PUPs with non-null F8 mutations developed inhibitors.

Conclusion In the NuProtect study, the rate of inhibitor development in PUPs with severe haemophilia A treated with simoctocog alfa was lower than the rate reported for hamster-cell-derived recombinant factor VIII products in other recent clinical trials. No inhibitors were reported in PUPs with non-null F8 mutations.

Keywords

coagulation - FVIII inhibitors - haemophilia

Author Contribbutions

R. J. Liesner designed the research, analysed the data and wrote the first draft of the manuscript. All authors provided input, reviewed and approved the manuscript.




Publication History

Received: 14 October 2020

Accepted: 04 December 2020

Article published online:
13 February 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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