Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials

Haemophilia. 2018 Nov;24(6):911-920. doi: 10.1111/hae.13608. Epub 2018 Sep 24.

Abstract

Introduction: Prophylaxis with replacement factor IX (FIX) reduces bleeding frequency and improves quality of life in haemophilia B patients. With prophylaxis, the likelihood of bleeding is lowered with increasing trough levels. New products with extended half-life (EHL) can maintain high factor activity levels over prolonged periods, compared with standard FIX products.

Aim: To evaluate the safety, efficacy and pharmacokinetics of the new recombinant FIX EHL product, nonacog beta pegol (N9-GP), using pooled data, with a focus on-but not limited to-prophylaxis at 40 IU/kg.

Methods: N9-GP has been investigated in males with congenital haemophilia B and FIX activity ≤2% in the paradigm™ clinical trial programme. This analysis includes pooled data from five completed paradigm™ trials conducted in previously treated adults, adolescents and children, focusing on results of prophylaxis with 40 IU/kg once-weekly intravenous dosing.

Results: In total, 115 previously treated patients were exposed to N9-GP. Of 54 patients (47%) treated with N9-GP 40 IU/kg once-weekly prophylaxis, 72% experienced no spontaneous bleeds over 1 year. In all patients receiving 40 IU/kg once-weekly, median overall annualized bleeding rate (ABR) was 1.03 (interquartile range 0.00; 2.89); median spontaneous ABR was 0.00 (0.00; 0.80). No patients developed inhibitors. Estimated mean steady-state trough levels with N9-GP 40 IU/kg once-weekly were ≥15% overall; 27.3% in adolescents and adults.

Conclusion: N9-GP 40 IU/kg once-weekly was well tolerated and effective in preventing bleeding, maintaining mean FIX activity levels ≥15% across all age groups. N9-GP may provide a new treatment option for preventing bleeding in haemophilia B patients.

Keywords: factor IX; haemophilia B; nonacog beta pegol; prophylaxis; target joint; trough level.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Factor IX / administration & dosage*
  • Factor IX / adverse effects
  • Factor IX / pharmacology*
  • Female
  • Hemophilia B / complications*
  • Hemorrhage / complications*
  • Hemorrhage / prevention & control*
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / pharmacology*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacology
  • Safety
  • Young Adult

Substances

  • Recombinant Proteins
  • nonacog beta pegol
  • Polyethylene Glycols
  • Factor IX

Grants and funding