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

## TL;DR

This study shows that long-term use of nonacog beta pegol in children with hemophilia B is safe and effective, with no negative effects on brain development.

## Contribution

The study provides the longest follow-up data on extended half-life factor IX prophylaxis in children with hemophilia B.

## Key findings

- No neurocognitive or neurologic concerns were observed in children using nonacog beta pegol for up to 8 years.
- High treatment adherence and low annualized bleeding rates were reported in both previously treated and previously untreated patients.
- Only 4 out of 50 previously untreated patients developed inhibitory antibodies.

## Abstract

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.

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.

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.

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.

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.

•Long-term safety data for clotting factor concentrates joined to polyethylene glycol molecules are limited.•Paradigm 5/6 assesses the long-term safety and efficacy of nonacog beta pegol in children with hemophilia B.•Safety data showed no impact of long-term nonacog beta pegol on neurologic or neurocognitive development.•Efficacy results were robust, with high treatment adherence and low bleeding rates.

Long-term safety data for clotting factor concentrates joined to polyethylene glycol molecules are limited.

Paradigm 5/6 assesses the long-term safety and efficacy of nonacog beta pegol in children with hemophilia B.

Safety data showed no impact of long-term nonacog beta pegol on neurologic or neurocognitive development.

Efficacy results were robust, with high treatment adherence and low bleeding rates.