Novel, human cell line‐derived recombinant factor VIII (human‐cl rhFVIII; Nuwiq^®) in adults with severe haemophilia A: efficacy and safety

Abstract

Introduction: Nuwiq â [human cell line-derived recombinant factor VIII (human-cl rhFVIII)] is a new generation rFVIII protein, without chemical modification or fusion to any other protein, produced in a human cell line. Aim/methods: This prospective, open-label, multinational phase III study assessed the efficacy and safety of human-cl rhFVIII in 32 adult previously treated patients (PTPs) with severe haemophilia A during standard prophylaxis for ≥6 months and ≥50 exposure days. Efficacy in treating bleeds and during surgical prophylaxis was also assessed. Results: Prophylactic efficacy, based on mean monthly bleeding rate, was rated as 'excellent' or 'good' in 97% of patients for all bleeds and in 100% of patients for spontaneous bleeds. Mean (SD) annualized bleeding rate was 2.28 (3.73) [median = 0.9] for all bleeds, 1.16 (2.57) [median = 0] for spontaneous bleeds and 1.00 (1.79) [median = 0] for traumatic bleeds. There were no bleeds in 50% of patients and there were no major, life-threatening bleeds. Efficacy was 'excellent' or 'good' in treating 28 (100%) of 28 bleeds. Overall efficacy was rated as 'excellent' during four surgical procedures (three major, one minor) and 'moderate' during one major surgery. Incremental in vivo recovery (IVR) data were comparable with the one-stage and chromogenic assays. IVR was >2.0% per IU kg À1 for all measurements and stable over 6 months. No patients developed FVIII inhibitors and there were no treatment-related serious or severe adverse events. Conclusion: These results in adult PTPs indicate that human-cl rhFVIII is effective for the prevention and treatment of bleeds in adults with severe haemophilia A.

Factor VIII products and inhibitor development in previously treated patients with severe or moderately severe hemophilia A: a systematic review

“…Eighty‐two unique articles were reviewed in full; of these, 52 articles were excluded. Thirty articles were selected for the analysis, and four additional articles were included after monthly searches on PubMed. Most articles reported on a single cohort of patients using one brand of rFVIII product, whereas three articles provided information on multiple cohorts.…”

“… reported on three cohorts using different rFVIII products. In total, 34 articles reporting on 41 cohorts were included . The characteristics of the 52 excluded articles are shown in Table S1, and references to the 52 excluded articles (labeled S1–S52) are also shown in Table S1.…”

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

“…15 Simoctocog alfa (Nuwiq) reported a median ABR of 0.9 in a small study of 32 adult patients; however, this bleeding rate was achieved with a prophylactic regimen requiring dosing every second day. 16 This study was designed to reflect clinical practice and as such, patients were assigned to prophylaxis regimens based on the clinical judgment of the treating physician. This resulted in one-third of the study population being assigned to a 2 times weekly prophylaxis regimen and half of the population being assigned to a 3 times weekly regimen.…”

Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A

“…60 To date, clinical studies with this human cell line-derived rFVIII, involving 59 and 32 previously treated children and adult hemophiliacs, respectively, have shown no FVIII inhibitors. 73,74 As the chaperone of FVIII in plasma, the role of VWF in FVIII immunogenicity cannot be ignored. It has been proposed that VWF may serve an immunoprotective role in 2 ways.…”