N9-GP in Previously Treated Pediatric Patients with Hemophilia B – Extended Follow-up

Introduction 

Severe hemophilia B is associated with frequent spontaneous bleeds. Primary prophylaxis in children with this form of hemophilia is the standard approach and involves the early initiation of regular administration of coagulation factor IX (FIX).

Extended half-life coagulation factor IX (EHL FIX) significantly reduces the burden of prophylactic treatment for hemophilia B caused by frequent intravenous applications. Among the EHL FIXs is also nonacog beta pegol (N9-GP), which has up to a 5-fold prolonged biological half-life compared to standard half-life factors.

Extended Follow-Up in the Paradigm 5 Study

Paradigm 5 was an international open-label Phase III study that evaluated the administration of N9-GP in children aged up to 12 years. These were previously treated patients with hemophilia B and FIX levels ≤ 2%. The N9-GP dosage was fixed at 40 IU/kg i.v. once weekly. The primary aim of the study was the incidence of FIX inhibitor.

Subsequently, an analysis of the extended 5-year follow-up and comparison with results after the first year of treatment (> 52 weeks of exposure) was published. The main phase of the study involved 25 participants, with 22 entering the extended phase. At data cutoff, 17 patients were still active in the study.

The median treatment duration was 5.6 years, with a median of 290 complete exposure days. None of the patients developed a FIX inhibitor. No new safety signals or thromboembolic events were observed during the extended follow-up. Neurological monitoring showed no abnormal findings.

Analysis Results

A total of 16 patients (64%) were free of spontaneous bleeds. When bleeds did occur, they were mild or moderate. 93% of bleeds were controlled with 1 or 2 injections of N9-GP. No cases of intracranial bleeding were reported.

The annual bleed rate (ABR) over 5 years was low (median/estimated average total ABR: 0.66/0.99) and decreased compared to the first year (1.00/1.44). The median/estimated average total spontaneous ABR was 0.00/0.45 in the first year and 0.00/0.33 in the fifth year. The average trough level of FIX was 17.9%. The average plasma concentration of polyethylene glycol (PEG) reached a steady state within 6 months and slightly increased over time in line with observed minimal plasma FIX levels.

Conclusion

This analysis demonstrated that N9-GP administered for ≥ 5 years has favorable long-term safety and effectiveness in previously treated pediatric patients with hemophilia B.

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Source: Carcao M., Kearney S., Lu M. Y. et al. Long-term safety and efficacy of nonacog beta pegol (N9-GP) administered for at least 5 years in previously treated children with hemophilia B. Thromb Haemost 2020; 120: 737–746, doi: 10.1055/s-0040-1709521.