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

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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® .

authors

  • Liesner, RJ
  • Abashidze, M
  • Aleinikova, O
  • Altisent, C
  • Belletrutti, MJ
  • Borel-Derlon, A
  • Carcao, M
  • Chambost, H
  • Chan, Anthony
  • Dubey, L
  • Ducore, J
  • Fouzia, NA
  • Gattens, M
  • Gruel, Y
  • Guillet, B
  • Kavardakova, N
  • El Khorassani, M
  • Klukowska, A
  • Lambert, T
  • Lohade, S
  • Sigaud, M
  • Turea, V
  • Wu, JKM
  • Vdovin, V
  • Pavlova, A
  • Jansen, M
  • Belyanskaya, L
  • Walter, O
  • Knaub, S
  • Neufeld, EJ

publication date

  • March 2018