Dataset Information

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

ABSTRACT: 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 (>150 exposure days) adults with congenital hemophilia B (FIX activity ?2%). Patients received single intravenous injections (50 IU/kg) of N9-GP and rFIXFc with at least 21 days between doses. Plasma FIX activity, predose, and at serial time points up to 240 hours 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 50 IU/kg (AUC0-inf,norm). Results:Fifteen patients received study treatment. Based on FIX activity results from the one-stage clotting assays, estimated AUC0-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 30 minutes and maximum FIX activity (dose-normalized to 50 IU/kg) and six times higher FIX activity at 168 hours 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. Registration:This trial is registered with clinicaltrials.gov (NCT03075670) and the European Clinical Trials Database (EudraCT: 2016-001149-25).

SUBMITTER: Escuriola Ettingshausen C

PROVIDER: S-EPMC6462750 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Escuriola Ettingshausen Carmen C Hegemann Inga I Simpson Mindy L ML Cuker Adam A Kulkarni Roshni R Pruthi Rajiv K RK Garly May-Lill ML Meldgaard Rikke M RM Persson Paula P Klamroth Robert R

Research and practice in thrombosis and haemostasis 20190323 2

<h4>Background and objective</h4>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.<h4>Patients/methods</h4>Paradigm 7 was a multicenter, open-label, randomized, crossover trial in previously treated (>150 exposure days) adults with congenital hemophilia B (FIX activity ≤2%). Patients received single intravenous injections (50 IU/kg) of N9-GP and rFIXFc w ...[more]

PMID: 31011711

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Project description:IntroductionProphylactic treatment of hemophilia B with recombinant factor IX (rFIX) molecules with enhanced pharmacokinetics including rIX-FP (albutrepenonacog alfa; Idelvion©) and rFIXFc (eftrenonacog alfa; Alprolix©) have commonly been used in the clinic. In the absence of head-to-head comparative trials, the aim of this study was to estimate the efficacy of rIX-FP versus rFIXFc using matching-adjusted indirect comparisons (MAICs).MethodsMAIC analyses leveraged individual patient data from the PROLONG-9FP trial and published summary-level data from the B-LONG trial for subjects who received weekly prophylaxis regimens. Individual patient data were used to assign weights and balance subjects from PROLONG-9FP with subjects from B-LONG on baseline disease severity, age, prior FIX regimen, and body mass index (BMI). Six efficacy outcomes were analyzed including annualized bleeding rate (ABR), annualized spontaneous bleeding rate (AsBR), annualized joint bleeding rate (AjBR), and the proportion of subjects without bleeding events (for total, spontaneous, and joint bleeding events).ResultsAfter adjustment for baseline disease severity, age, prior FIX regimen, and BMI, rIX-FP was associated with a statistically significant decrease in AsBR (rate ratio [RR] 0.42; 95% confidence interval [CI] 0.22, 0.82; P = 0.0107), and the proportion of patients without bleeding events (odds ratio [OR] 3.24; 95% CI 1.41, 7.45; P = 0.0057), spontaneous bleeding events (OR 3.47; 95% CI 1.56, 7.73; P = 0.0023), and joint bleeding events (OR 2.41; 95% CI 1.10, 5.26; P = 0.0274) compared with rFIXFc. Prophylactic treatment with rIX-FP was also associated with a numerically lower ABR (RR 0.75; 95% CI 0.32, 1.75; P = 0.5095) and AjBR (RR 0.82; 95% CI 0.37, 1.82; P = 0.6178).ConclusionThe MAICs demonstrated that weekly prophylaxis treatment of severe hemophilia B with rIX-FP resulted in favorable efficacy outcomes as compared to rFIXFc. These findings suggest rIX-FP may offer improved clinical benefits over rFIXFc.

Dataset Information

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

Publications

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

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