Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study

R. J. Liesner, M. Abashidze, O. Aleinikova, C. Altisent, M. J. Belletrutti, A. Borel-Derlon, M. Carcao, H. Chambost, A. K.C. Chan, L. Dubey, Jonathan M Ducore, N. A. Fouzia, M. Gattens, Y. Gruel, B. Guillet, N. Kavardakova, M. El Khorassani, A. Klukowska, T. Lambert, S. LohadeM. Sigaud, V. Turea, J. K.M. Wu, V. Vdovin, A. Pavlova, M. Jansen, L. Belyanskaya, O. Walter, S. Knaub, E. J. Neufeld

Research output: Contribution to journalArticle

15 Scopus citations

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®.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalHaemophilia
Volume24
Issue number2
DOIs
StatePublished - Mar 1 2018

Keywords

  • FVIII inhibitors
  • haemophilia A
  • Human-cl rhFVIII
  • Nuwiq
  • previously untreated patients

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

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    Liesner, R. J., Abashidze, M., Aleinikova, O., Altisent, C., Belletrutti, M. J., Borel-Derlon, A., Carcao, M., Chambost, H., Chan, A. K. C., Dubey, L., Ducore, J. M., Fouzia, N. A., Gattens, M., Gruel, Y., Guillet, B., Kavardakova, N., El Khorassani, M., Klukowska, A., Lambert, T., ... Neufeld, E. J. (2018). Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study. Haemophilia, 24(2), 211-220. https://doi.org/10.1111/hae.13320