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Immunogenicity, efficacy and safety of Nuwiq ® (human‐cl rh FVIII ) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study
Author(s) -
Liesner R. J.,
Abashidze M.,
Aleinikova O.,
Altisent C.,
Belletrutti M. J.,
BorelDerlon A.,
Carcao M.,
Chambost H.,
Chan A. K. C.,
Dubey L.,
Ducore J.,
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.
Publication year - 2018
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.13320
Subject(s) - medicine , immunogenicity , haemophilia , tolerability , interim analysis , haemophilia a , cumulative incidence , confidence interval , incidence (geometry) , adverse effect , clinical trial , surgery , cohort , immunology , antibody , physics , optics
Nuwiq ® (Human‐cl rh FVIII ) 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 ( PUP s) with severe HA are being assessed in the ongoing NuProtect study. Methods The study, conducted across 38 centres worldwide, is evaluating 110 true PUP s of all ages and ethnicities enrolled for study up to 100 exposure days ( ED s) 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 PUP s with ≥20 ED s from a preplanned interim analysis were analysed. High‐titre ( HT ) inhibitors developed in 8 of 66 patients after a median of 11.5 ED s (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 PUP s treated with Nuwiq ® .