Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A

Bayer, Whippany, USA. Bayer, Berlin, Germany. Bayer, Wuppertal, Germany. LAP&P Consultants BV, Leiden, the Netherlands. Centre for Thrombosis and Haemostasis, Lund University, Skane University Hospital, Malmo, Sweden. Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. Department of Health Research Methods, Evidence and Impact, and Department of Medicine, McMaster University, Hamilton, Canada. Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy. Specialized Hospital for Active Treatment, Sofia, Bulgaria.

Annals of hematology. 2019
BAY 94-9027 is an extended-half-life, recombinant factor VIII (rFVIII) product conjugated with a 60-kDa branched polyethylene glycol (PEG) molecule indicated for use in previously treated patients (aged ≥ 12 years) with hemophilia A. This randomized, open-label, two-way crossover study compared the pharmacokinetics (PK) of BAY 94-9027 and rFVIII Fc fusion protein (rFVIIIFc) in patients with hemophilia A. Patients aged 18-65 years with FVIII < 1% and ≥ 150 exposure days to FVIII were randomized to receive intravenous single-dose BAY 94-9027 60 IU/kg followed by rFVIIIFc 60 IU/kg or vice versa, with ≥ 7-day wash-out between doses. FVIII activity was measured by one-stage assay. PK parameters, including area under the curve from time 0 to the last data point (AUClast, primary parameter), half-life, and clearance were calculated. Eighteen patients were randomized and treated. No adverse events were observed. In the analysis set excluding one outlier, geometric mean (coefficient of variation [%CV, 95% confidence interval {CI}]) AUClast was significantly higher for BAY 94-9027 versus rFVIIIFc (2940 [37.8, 2440-3550] IU h/dL versus 2360 [31.8, 2010-2770] IU h/dL, p = 0.0001). A population PK model was developed to simulate time to reach FVIII threshold levels; median time to 1 IU/dL was approximately 13 h longer for BAY 94-9027 versus rFVIIIFc after a single infusion of 60 IU/kg. In conclusion, BAY 94-9027 had a superior PK profile versus rFVIIIFc. : NCT03364998.
Study details
Language : eng
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