PB0657 - Up to 6 years of once-weekly prophylactic dosing of nonacog beta pegol (N9-GP) was associated with high adherence, with a low incidence of spontaneous bleeds in children with hemophilia B

Background: Nonacog beta pegol (N9-GP) is a recombinant factor IX (FIX) with an extended half-life that minimizes treatment burden by reducing dosing frequency while maintaining high FIX trough levels with once-weekly dosing.

Aims: To report updated data from the ongoing main and extension phases of paradigm6 (NCT02141074), an open-label phase III trial evaluating N9-GP prophylaxis in previously untreated children with hemophilia B.

Methods: The study included previously untreated males aged < 6 years with hemophilia B (FIX activity level ≤2%); up to three exposure days (EDs) to FIX-containing products prior to enrollment. Patients received N9-GP 40 IU/kg once weekly (prophylaxis) with an optional on-demand or slow start-up of prophylaxis up to 24 months of age or 20 EDs, whichever came first (pre-prophylaxis). Key treatment outcomes were incidence of anti-FIX inhibitory antibodies (≥0.6 Bethesda units), annualized bleeding rates (ABRs), N9-GP consumption, hemostatic response for treatment of bleeds, FIX trough levels, and patient adherence (defined as percentage of all administered prophylactic doses taken within 6–8 days of previous prophylactic dose).

Results: Figure 1 shows numbers of patients at each trial stage. The inhibitor incidence rate was 8%. Adherence to N9-GP prophylaxis was high (96.1%). The overall hemostatic success rate was high (96.4%). Table 1 summarizes further key efficacy outcomes for patients on N9-GP prophylaxis. Notably, both overall and spontaneous ABRs were low (medians of 0.25 and 0.00, respectively), and most bleeds (88.3%) required only one injection. Furthermore, mean steady-state FIX trough levels (15.6 IU/dL) were within the range of mild hemophilia; no patients developed target joints.

Conclusion(s): This updated analysis provides additional data on the long-term (up to 6.11 years) outcomes following N9-GP prophylaxis. The low inhibitor incidence, favorable ABRs for prophylactic treatment, no target joint development, and high adherence demonstrate the continued efficacy of once-weekly N9-GP in children with hemophilia B.