Phase I study of BAY 94‐9027, a PEGylated B‐domain‐deleted recombinant factor VIII with an extended half‐life, in subjects with hemophilia A. (April 2014)

• Record Type: Journal Article
• Authors: Coyle, T. E.; Reding, M. T.; Lin, J. C.; Michaels, L. A.; Shah, A.; Powell, J.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 12:Number 4(2014:Apr.)
• Page Start: 488
• Page End: 496
• Publication Date: 2014-04
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12506
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12506-abs-0001"> <title>Summary</title> <sec id="jth12506-sec-0001" sec-type="section"> <title>Background</title> <p>BAY 94‐9027 is a B‐domain‐deleted recombinant factor VIII (rFVIII) with site‐specific attachment of poly(ethylene glycol) that has shown an extended half‐life in animal models of hemophilia.</p> </sec> <sec id="jth12506-sec-0002" sec-type="section"> <title>Objectives</title> <p>To assess the pharmacokinetics and safety of BAY 94‐9027 after single and repeated administration in subjects with severe hemophilia A.</p> </sec> <sec id="jth12506-sec-0003" sec-type="section"> <title>Patients/Methods</title> <p>This 8‐week, prospective, multicenter, open‐label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3‐day washout, subjects received a single dose of sucrose‐formulated rFVIII (rFVIII‐FS) (cohort 1 [<italic>n </italic>=<italic> </italic>7], 25 IU kg<sup>−1</sup>; cohort 2 [<italic>n </italic>=<italic> </italic>7], 50 IU kg<sup>−1</sup>) for a 48‐h pharmacokinetic (PK) study. After another ≥ 3‐day washout, cohort 1 received twice‐weekly BAY 94‐9027 at 25 IU kg<sup>−1</sup> (16 doses), and cohort 2 received once‐weekly BAY 94‐9027 at 60 IU kg<sup>−1</sup> (nine doses). A 168‐h PK study was performed after the first and last BAY 94‐9027 doses.</p> </sec> <sec id="jth12506-sec-0004" sec-type="section"> <title>Results</title> <p>BAY 94‐9027 showed equivalent recovery and an improved PK profile vs. rFVIII‐FS, with a half‐life of ~ 19 h (vs. ~ 13.0 h for rFVIII‐FS). BAY 94‐9027 was well tolerated, and no immunogenicity was observed.</p> </sec> <sec id="jth12506-sec-0005" sec-type="section"> <title>Conclusions</title> <p>This phase I study demonstrates that BAY 94‐9027 has an extended half‐life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8‐week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half‐life will permit less frequent prophylaxis dosing for patients with hemophilia.</p> </sec> </abstract>