Immunogenicity, efficacy and safety of Nuwiq ? ? (human‐cl rh FVIII FVIII ) in previously untreated patients with severe haemophilia A—Interim results from the NuProtect Study

摘要

Introduction 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 ? .