PK‐guided personalized prophylaxis with Nuwiq^® (human‐cl rhFVIII) in adults with severe haemophilia A

Abstract

Introduction: Nuwiq â (human-cl rhFVIII) is a 4 th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods: This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq â in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1-3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two-or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results: The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1. .1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg À1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion: PK-guided personalized prophylaxis with Nuwiq â provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.

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.…”

Individual thrombin generation and spontaneous bleeding rate during personalized prophylaxis with Nuwiq® (human‐cl rhFVIII) in previously treated patients with severe haemophilia A

“…Nuwiq ® is produced in a human cell line and thus exhibits human‐specific post‐translational modifications and is without chemical modification or fusion with other protein . The pharmacokinetics (PK), safety and efficacy of personalized prophylaxis with Nuwiq ® were examined in GENA‐21, a prospective, phase IIIb study in 66 previously treated adults with severe haemophilia A . One patient was excluded from the efficacy analysis as he had 79 bleeds during the study and was a major outlier.…”

“…During personalized prophylaxis, 73% of patients did not experience any bleeding episodes and 83% of patients did not experience spontaneous bleeds. The median dosing interval was extended to 3.5 days, and 57% of patients (n = 65) were treated with ≤2 infusions of FVIII per week …”

Long‐term tolerability, immunogenicity and efficacy of Nuwiq® (human‐cl rhFVIII) in children with severe haemophilia A

“…Nuwiq ® is fully sulphated, which ensures a high affinity to circulating von Willebrand factor, contains only human glycans and is therefore devoid of potentially antigenic nonhuman epitopes present in rFVIII derived from hamster cell lines . In patients with haemophilia A, Nuwiq ® has been shown to be effective in the treatment and prevention of bleeds and in surgical prophylaxis in adults and children . The efficacy and safety of Nuwiq ® in children with severe haemophilia A was demonstrated in a prospective phase III multinational clinical study (GENA‐03) and reported previously in this journal .…”