PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A

T. Lissitchkov, L. Rusen, P. Georgiev, J. Windyga, R. Klamroth, L. Gercheva, L. Nemes, A. Tiede, J. Bichler, S. Knaub, L. Belyanskaya, O. Walter, K. J. Pasi

Research output: Article

14 Citations (Scopus)

Abstract

Introduction: Nuwiq® (human-cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1–3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion: PK-guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.

Original languageEnglish
Pages (from-to)697-704
Number of pages8
JournalHaemophilia
Volume23
Issue number5
DOIs
Publication statusPublished - szept. 1 2017

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Hemophilia A
Pharmacokinetics
Hemorrhage
Uncertainty
Joints
Safety
Cell Line
Proteins
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

Lissitchkov, T., Rusen, L., Georgiev, P., Windyga, J., Klamroth, R., Gercheva, L., ... Pasi, K. J. (2017). PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A. Haemophilia, 23(5), 697-704. https://doi.org/10.1111/hae.13251

PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A. / Lissitchkov, T.; Rusen, L.; Georgiev, P.; Windyga, J.; Klamroth, R.; Gercheva, L.; Nemes, L.; Tiede, A.; Bichler, J.; Knaub, S.; Belyanskaya, L.; Walter, O.; Pasi, K. J.

In: Haemophilia, Vol. 23, No. 5, 01.09.2017, p. 697-704.

Research output: Article

Lissitchkov, T, Rusen, L, Georgiev, P, Windyga, J, Klamroth, R, Gercheva, L, Nemes, L, Tiede, A, Bichler, J, Knaub, S, Belyanskaya, L, Walter, O & Pasi, KJ 2017, 'PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A', Haemophilia, vol. 23, no. 5, pp. 697-704. https://doi.org/10.1111/hae.13251
Lissitchkov T, Rusen L, Georgiev P, Windyga J, Klamroth R, Gercheva L et al. PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A. Haemophilia. 2017 szept. 1;23(5):697-704. https://doi.org/10.1111/hae.13251
Lissitchkov, T. ; Rusen, L. ; Georgiev, P. ; Windyga, J. ; Klamroth, R. ; Gercheva, L. ; Nemes, L. ; Tiede, A. ; Bichler, J. ; Knaub, S. ; Belyanskaya, L. ; Walter, O. ; Pasi, K. J. / PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A. In: Haemophilia. 2017 ; Vol. 23, No. 5. pp. 697-704.
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abstract = "Introduction: Nuwiq{\circledR} (human-cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq{\circledR} in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1–3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results: The median dosing interval during personalized prophylaxis was 3.5 days, with 57{\%} of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1{\%} of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2{\%} from 100.0 to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion: PK-guided personalized prophylaxis with Nuwiq{\circledR} provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.",
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T1 - PK-guided personalized prophylaxis with Nuwiq® (human-cl rhFVIII) in adults with severe haemophilia A

AU - Lissitchkov, T.

AU - Rusen, L.

AU - Georgiev, P.

AU - Windyga, J.

AU - Klamroth, R.

AU - Gercheva, L.

AU - Nemes, L.

AU - Tiede, A.

AU - Bichler, J.

AU - Knaub, S.

AU - Belyanskaya, L.

AU - Walter, O.

AU - Pasi, K. J.

PY - 2017/9/1

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N2 - Introduction: Nuwiq® (human-cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1–3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion: PK-guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.

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KW - haemophilia A

KW - human-cl rhFVIII

KW - Nuwiq

KW - personalized prophylaxis

KW - pharmacokinetics

KW - recombinant FVIII

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