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. Lohade & 10 others M. 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

10 Citations (Scopus)

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

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Hemophilia A
Safety
Incidence
Confidence Intervals
Hemorrhage
Cell Line
Proteins

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Liesner, R. J., Abashidze, M., Aleinikova, O., Altisent, C., Belletrutti, M. J., Borel-Derlon, A., ... 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

Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study. / 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, Jonathan M; Fouzia, N. A.; Gattens, M.; Gruel, Y.; Guillet, B.; Kavardakova, N.; El Khorassani, M.; Klukowska, A.; Lambert, T.; Lohade, S.; Sigaud, M.; Turea, V.; Wu, J. K.M.; Vdovin, V.; Pavlova, A.; Jansen, M.; Belyanskaya, L.; Walter, O.; Knaub, S.; Neufeld, E. J.

In: Haemophilia, Vol. 24, No. 2, 01.03.2018, p. 211-220.

Research output: Contribution to journalArticle

Liesner, RJ, Abashidze, M, Aleinikova, O, Altisent, C, Belletrutti, MJ, Borel-Derlon, A, Carcao, M, Chambost, H, Chan, AKC, Dubey, L, Ducore, JM, 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 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, vol. 24, no. 2, pp. 211-220. https://doi.org/10.1111/hae.13320
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, Jonathan M ; Fouzia, N. A. ; Gattens, M. ; Gruel, Y. ; Guillet, B. ; Kavardakova, N. ; El Khorassani, M. ; Klukowska, A. ; Lambert, T. ; Lohade, S. ; Sigaud, M. ; Turea, V. ; Wu, J. K.M. ; Vdovin, V. ; Pavlova, A. ; Jansen, M. ; Belyanskaya, L. ; Walter, O. ; Knaub, S. ; Neufeld, E. J. / Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study. In: Haemophilia. 2018 ; Vol. 24, No. 2. pp. 211-220.
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abstract = "Introduction: Nuwiq{\circledR} (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{\circledR} in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq{\circledR} 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{\circledR} (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{\circledR}.",
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T1 - Immunogenicity, efficacy and safety of Nuwiq® (human-cl rhFVIII) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study

AU - Liesner, R. J.

AU - Abashidze, M.

AU - Aleinikova, O.

AU - Altisent, C.

AU - Belletrutti, M. J.

AU - Borel-Derlon, A.

AU - Carcao, M.

AU - Chambost, H.

AU - Chan, A. K.C.

AU - Dubey, L.

AU - Ducore, Jonathan M

AU - Fouzia, N. A.

AU - Gattens, M.

AU - Gruel, Y.

AU - Guillet, B.

AU - Kavardakova, N.

AU - El Khorassani, M.

AU - Klukowska, A.

AU - Lambert, T.

AU - Lohade, S.

AU - Sigaud, M.

AU - Turea, V.

AU - Wu, J. K.M.

AU - Vdovin, V.

AU - Pavlova, A.

AU - Jansen, M.

AU - Belyanskaya, L.

AU - Walter, O.

AU - Knaub, S.

AU - Neufeld, E. J.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - 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®.

AB - 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®.

KW - FVIII inhibitors

KW - haemophilia A

KW - Human-cl rhFVIII

KW - Nuwiq

KW - previously untreated patients

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