Nuwiq® (Human-cl rhFVIII) is a fourth generation recombinant FVIII. This is an ongoing, prospective, multicentre, multinational, open-label, non-controlled, phase III study (NuProtect study) of 110 male previously untreated patients, which aimed to assess immuno-genicity, efficacy and safety of Nuwiq in severe Hemophilia A patients. Here, they report data from a subgroup of 66 patients treated with Nuwiq for up to 100 exposure days (EDs) or 5 years.
Patients received Nuwiq for standard prophylaxis or on-demand treatment, and for treatment of breakthrough bleeds or surgical prophylaxis, as required. The recommended dose for standard prophylaxis was 20-50 U FVIII/kg. The dosage and duration for treating breakthrough bleeds, on-demand treatment and during surgical prophylaxis depended on the location and extent of bleeding, and the clinical condition of the patient. 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.
High-titre (HT) inhibitors developed in 8 of 66 patients after a median of 11.5 EDs (range 6-24) and low-titre inhibitors in 5 patients. Cumulative incidence was 12.8% for HT inhibitors and 20.8% for all inhibitors. Efficacy was rated as “excellent” or “good” in treating 91.8% of bleeds and for 8 (89%) procedures. Nuwiq was generally well tolerated. The majority of AEs were mild.
Interim analysis included only the 66 patients who were treated for ≥20 EDs with Nuwiq. As almost all patients enrolled across 14 countries in this interim analysis were Caucasian, no data were collected for patients of African descent who are assumed to be at higher risk of inhibitor development.