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PK ‐guided personalized prophylaxis with Nuwiq ® (human‐cl rh FVIII ) in adults with severe haemophilia A
Author(s) -
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.
Publication year - 2017
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13251
Subject(s) - medicine , dosing , interquartile range , regimen , haemophilia a , haemophilia , adverse effect , pharmacokinetics , phases of clinical research , clinical trial , surgery
Nuwiq ® (human‐cl rh FVIII ) is a 4 th 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 III b 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.