Favorable pharmacokinetics in hemophilia B for nonacog beta pegol versus recombinant factor IX-Fc fusion protein: A randomized trial

Background and Objective: Nonacog beta pegol (N9-GP) and recombinant factor IX-Fc fusion protein (rFIXFc) are extended half-life rFIX compounds. We report the first single-dose pharmacokinetic trial of N9-GP and rFIXFc. Patients/Methods: Paradigm 7 was a multicenter, open-label, randomized, crossover trial in previously treated (>150exposure days) adults with congenital hemophilia B (FIX activity 2%). Patients received single intravenous injections (50IU/kg) of N9-GP and rFIXFc with at least 21days between doses. Plasma FIX activity, predose, and at serial time points up to 240hours postdose, was measured using validated one-stage clotting assays (SynthAFax for N9-GP; Actin FSL for rFIXFc) and a chromogenic assay (ROX factor IX) with normal human plasma as calibrator. The primary endpoint was area under the FIX activity-time curve from 0 to infinity, dose-normalized to 50IU/kg (AUC(0-inf,norm)). Results: Fifteen patients received study treatment. Based on FIX activity results from the one-stage clotting assays, estimated AUC(0-inf,norm) was significantly greater for N9-GP than rFIXFc (ratio: 4.39; P<0.0001, based on a two-sided test on 5% significance level). In addition, N9-GP had a longer terminal half-life, two times higher incremental recovery at 30minutes and maximum FIX activity (dose-normalized to 50IU/kg) and six times higher FIX activity at 168hours than rFIXFc. These findings were largely comparable with the chromogenic assay data and are consistent with published data for each compound. Conclusions: In this comparison, N9-GP demonstrated favorable pharmacokinetic characteristics versus rFIXFc, helping clinicians to understand differences between N9-GP and rFIXFc.