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

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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. 2017

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ASJC Scopus subject areas

  • Hematology
  • Genetics(clinical)

Cite this

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. (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