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patients (patients with ≥ 10 EDs plus patients who developed inhibitors) developed high‐titer inhibitors and were withdrawn.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.