Nonacog beta pegol prophylaxis in children with hemophilia B: safety, efficacy, and neurodevelopmental outcomes for up to 8 years

Karin S Walsh; Christine Mrakotsky; Manuel Carcao; Anthony K C Chan; Pernille Højlund Nielsen; Helle Holst; Kevin Shapiro

doi:10.1016/j.rpth.2024.102341

Nonacog beta pegol prophylaxis in children with hemophilia B: safety, efficacy, and neurodevelopmental outcomes for up to 8 years

Res Pract Thromb Haemost. 2024 Feb 8;8(2):102341. doi: 10.1016/j.rpth.2024.102341. eCollection 2024 Feb.

Authors

Karin S Walsh¹, Christine Mrakotsky², Manuel Carcao³, Anthony K C Chan⁴, Pernille Højlund Nielsen⁵, Helle Holst⁵, Kevin Shapiro⁶

Affiliations

¹ Center for Neuroscience and Behavioral Medicine, Children's National Hospital and the George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
² Departments of Neurology & Psychiatry, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Division of Haematology/Oncology, Department of Paediatrics, the Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Department of Paediatrics, McMaster Centre for Transfusion Research, McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada.
⁵ Novo Nordisk A/S, Copenhagen, Denmark.
⁶ Cortica Healthcare and Children's Hospital Los Angeles, Westlake Village, California, USA.

Abstract

Background: Nonacog beta pegol (N9-GP) is an extended half-life PEGylated factor (F)IX product with established efficacy and short-term safety in persons with hemophilia B (HB). Long-term safety has been evaluated for polyethylene glycol exposure but not N9-GP.

Objectives: To assess safety, neurodevelopmental, and efficacy outcomes of children with HB receiving N9-GP prophylaxis across 2 open-label, single-arm, phase 3 studies: paradigm5 (previously treated patients [PTPs]) and paradigm6 (previously untreated patients [PUPs]) in this interim analysis.

Methods: PTPs (aged ≤12 years) and PUPs (aged <6 years) with severe/moderate (≤2% FIX level) HB were recruited to N9-GP prophylaxis (40 IU/kg once weekly) in paradigm5 and paradigm6, respectively. Safety assessments included FIX inhibitor incidence, adverse events, neurocognitive and neurologic outcomes, polyethylene glycol concentration in plasma, and medical events of special interest. Efficacy endpoints included bleeds, N9-GP hemostatic effect, and FIX consumption.

Results: Overall, 25 patients in paradigm5 and 50 patients in paradigm6 received N9-GP and were followed for up to 8 and 6 years, respectively. No inhibitory antibodies were reported in PTPs; 4 of the 50 PUPs developed inhibitors. Extensive evaluation revealed no neurocognitive or neurologic concerns with N9-GP use in children during the study period. Across both studies, few adverse events were reported as possibly related to N9-GP. High hemostatic response rate, high treatment adherence, low annualized bleeding rates, and no new target joints were reported.

Conclusion: These data provide the longest follow-up for an extended half-life FIX and confirm the long-term efficacy of N9-GP prophylaxis in children with HB with no observed neurocognitive or neurologic safety concerns.

Keywords: PEG; bleed; children; hemophilia B; nonacog beta pegol.