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

Abstract

Introduction Nuwiq® (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® in 201 previously treated patients with haemophilia A (HA). The immunogenicity, efficacy and safety of Nuwiq® in previously untreated patients (PUPs) with severe HA are being assessed in the ongoing NuProtect study. Methods The 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 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 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. Conclusion These interim data show a cumulative incidence of 12.8% for HT inhibitors and convincing efficacy and tolerability in PUPs treated with Nuwiq®.

Estimation of Nuwiq®(simoctocog alfa) activity using one‐stage and chromogenic assays—Results from an international comparative field study

“…Nuwiq ® (simoctocog alfa, human‐cl rhFVIII; Octapharma) is a fourth‐generation BDD rFVIII produced in a human cell line with human‐like post‐translational protein processing and without chemical modification or fusion to any other protein . Nuwiq ® is effective in the prevention and treatment of bleeds and for bleeding management during surgery in adults and children with haemophilia A and has demonstrated low immunogenicity in previously untreated patients …”

“…17,18 Nuwiq ® is effective in the prevention and treatment of bleeds and for bleeding management during surgery in adults and children with haemophilia A [19][20][21] and has demonstrated low immunogenicity in previously untreated patients. 22 The aim of this field study was to assess whether Nuwiq ® activity can be accurately measured with a variety of OSAs and CSAs used in routine laboratory practice. as to the identity of the concentrates and the target concentrations.…”

Continuous infusion of simoctocog alfa in haemophilia A patients undergoing surgeries

“…Simoctocog alfa is a 4th generation recombinant FVIII produced in a human cell line without chemical modification or fusion with any other protein, and simoctocog alfa is expressing human‐specific post‐translational modifications with the aim of reducing immunogenicity …”

“…Simoctocog alfa is a 4th generation recombinant FVIII produced in a human cell line without chemical modification or fusion with any other protein, and simoctocog alfa is expressing humanspecific post-translational modifications with the aim of reducing immunogenicity. 6,7 Clinical studies show that simoctocog alfa is highly effective in the treatment and prevention of bleeding episodes in previously treated adults and children, including those undergoing surgery. [8][9][10] A recent analysis with pooled data from seven clinical studies examined the safety and efficacy of simoctocog alfa in surgical prophylaxis.…”

How I approach: Previously untreated patients with severe congenital hemophilia A

“…For example, human‐cl rhFVIII (Nuwiq, Octapharma, Hoboken, NJ, USA) is a bioengineered rFVIII product which is produced in human cell lines as compared with the majority of products produced in animal cell lines. Published data from an interim analysis of the product in 66 PUPs with ≥20 EDs demonstrated that 20.8% had an inhibitor with 12.8% developing high‐titer inhibitors . In addition, emerging data suggest that recombinant FVIII Fc fusion protein (rFVIIIFc), a bioengineered factor product including B‐domain deleted FVIII fused to the Fc domain of Human IgG1, may be less immunogenic than other products due to properties of the attached Fc …”