A Clinical Study in Previously Untreated Patients with Severe Haemophilia A - Immunogenicity, Efficacy and Safety of Treatment with Human-Cl Rhfviii

IntroductionNuwiq((R)) (Human-cl rhFVIII) 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((R)) in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq((R)) in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. MethodsThe study, conducted across 38 centres worldwide, is evaluating 110 true PUPs of all ages and ethnicities enrolled for study up to 100 exposure days (EDs) or 5years maximum. The primary objective is to assess the immunogenicity of Nuwiq((R)) (inhibitor activity 0.6 BU) using the Nijmegen-modified Bethesda assay at a central laboratory. ResultsData for 66 PUPs with 20 EDs from a preplanned interim analysis were analysed. High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (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. ConclusionThese interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq((R)).