Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study

Abstract

Introduction FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line. Methods The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs. NuProtect was a prospective, multinational, open-label, non-controlled, phase III study. PUPs with severe haemophilia A (FVIII:C <1%) of any age and ethnicity were treated with simoctocog alfa for 100 exposure days or a maximum of 5 years. Patients were true PUPs without prior exposure to FVIII concentrates or blood components. Inhibitor titres were measured with the Nijmegen-modified Bethesda assay; cut-off for positivity was 0.6 BU mL−1 (≥0.6 to <5 low-titre, ≥5 high titre). Results A total of 108 PUPs with a median age at first treatment of 12.0 months (interquartile range: 8.0–23.5) were treated with simoctocog alfa. F8 mutation type was known for 102 patients (94.4%) of whom 90 (88.2%) had null F8 mutations and 12 (11.8%) had non-null mutations. Of 105 PUPs evaluable for inhibitor development, 28 (26.7%) developed inhibitors; 17 high titre (16.2%) and 11 low titre (10.5%). No PUPs with non-null F8 mutations developed inhibitors. Conclusion In the NuProtect study, the rate of inhibitor development in PUPs with severe haemophilia A treated with simoctocog alfa was lower than the rate reported for hamster-cell-derived recombinant factor VIII products in other recent clinical trials. No inhibitors were reported in PUPs with non-null F8 mutations.

Prophylaxis in children with haemophilia in an evolving treatment landscape

“…21 However, this trial did not include new-generation rFVIII products such as simoctocog alfa and efmoroctocog alfa, for which inhibitor incidences in PUPs may differ. 50 No class differences have been reported from the PedNet registry, 22 and a recent study showed that the risk of inhibitor development appears not to be linked to the class of CFC but is, rather, influenced by the treatment regimen used during the first 50 days of exposure to CFC: In PUPs with severe haemophilia A, the risk of inhibitor development is significantly higher with early, intensive peak treatment or on-demand treatment than with prophylaxis. 51,52 Prophylaxis with emicizumab is expected to delay the patient's exposure to FVIII CFC, and therefore it may take many years to reach 50 exposure days, currently the main period of risk for inhibitor development.…”

Personalised Prophylaxis in a Child with Haemophilia A and Type 1 Diabetes

“…For patients treated with the rFVIII described in the case study, two options exist to personalise treatment, either based on individual pharmacokinetic (PK) parameters [6] or on a population PK model [19]. Together with the low infusion volume, excellent efficacy in the prevention of bleeding [6] and a demonstrated low immunogenicity, [20] this makes this rFVIII an attractive option to satisfy the diverse demands HA patients may have.…”

Thrombosis and Haemostasis 2021 Editors' Choice Papers

“…The fourth generation rFVIII product simoctocog alfa (Nuwiq; Octapharma) replicating the native human FVIII protein without incorporation of potentially immunogenic elements of animal cell origin may represent a promising candidate to overcome this issue as reflected by the final data of the NuProtect study. 85 The recently approved bispecific monoclonal antibody emicizumab represents another very attractive approach for treating hemophilia A patients bypassing FVIII activation. We highlighted last year the published promising clinical trials and preliminary reports with emicizumab 86 as well as its cost-effectiveness and budget.…”