Nonacog beta pegol (N9‐GP) in hemophilia B: First report on safety and efficacy in previously untreated and minimally treated patients

Background/Objective We report the first analysis of an extended half-life recombinant factor IX, nonacog beta pegol (N9-GP), in previously untreated patients (PUPs) and minimally treated patients with hemophilia B. Methods Paradigm 6 (Safety and Efficacy of Nonacog Beta Pegol [N9-GP] in Previously Untreated Patients With Haemophilia B) is a multicenter, open-label, single-arm, phase 3 trial. Main inclusion criteria were males aged < 6 years, with hemophilia B with factor IX (FIX) activity ≤ 2%, who were previously untreated or with ≤ 3 exposure days (EDs) to FIX-containing products. Patients received N9-GP 40 IU/kg once weekly (prophylaxis) or individualized dosing (preprophylaxis). Bleeds were treated with N9-GP 40 IU/kg (80 IU/kg if severe). The primary end point was incidence of anti-FIX inhibitory antibodies (inhibitors). Secondary end points included safety outcomes and annualized bleeding rate (ABR). Results At data cutoff (August 31, 2018), 38 patients had been screened, and 37 had received N9-GP (median age, 1.0 years [range, 0-4]). Total in-trial EDs amounted to 2833, representing ~ 65 patient-years. Two (6.1%) of 33 "at-risk" patients (patients with ≥ 10 EDs plus patients who developed inhibitors) developed high-titer inhibitors and were withdrawn. No other safety concerns, including thromboembolic events, were identified. In the prophylaxis group (n = 28), 67.9% were bleed free; all bleeds (n = 15) were treated with one N9-GP injection; and overall, spontaneous, and traumatic ABRs were low (median ABRs of 0.0, 0.0, and 0.0, respectively; modeled mean ABRs of 0.31, 0.08, and 0.23, respectively). Estimated mean FIX trough activity was 15.0%. Conclusion We report an inhibitor incidence of 6.1%, which is within the expected range for PUPs with hemophilia B. No other safety concerns were identified; moreover, N9-GP provided effective hemostatic coverage.