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

Background Nonacog beta pegol (N9-GP) is an extended half-life PEGylated factor IX (FIX) product with established efficacy and short-term safety in patients with hemophilia B (HB). Long-term safety has been evaluated for polyethylene glycol (PEG) exposure, but not N9-GP. Objectives Assess safety, neurodevelopmental, and efficacy outcomes of children with HB (CwHB) receiving N9-GP prophylaxis across two 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 (AEs), neurocognitive and neurological outcomes, PEG 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 in paradigm6 received N9-GP and were followed for up to 8 and 6 years, respectively. No inhibitory antibodies were reported in PTPs; 4/50 PUPs developed inhibitors. Extensive evaluation revealed no neurocognitive or neurological concerns with N9-GP use in children during the study period. Across both studies, few AEs 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. Conclusions These data provide the longest follow-up for an extended half-life FIX and confirm the long-term efficacy of N9-GP prophylaxis in CwHB, with no observed neurocognitive or neurological safety concerns.