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Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa

2023; Elsevier BV; Volume: 7; Issue: 4 Linguagem: Inglês

10.1016/j.rpth.2023.100176

2475-0379

Toshko Lissitchkov, Annemieke Willemze, Christelle Jan, Moshe Zilberstein, Suresh Katragadda,

Blood Coagulation and Thrombosis Mechanisms

BackgroundEfanesoctocog alfa is a new class of factor (F) VIII replacement therapy designed to provide high sustained factor levels for longer by overcoming the von Willebrand factor half-life ceiling.ObjectivesTo assess the pharmacokinetics and safety of standard half-life (octocog alfa) and extended half-life (rurioctocog alfa pegol) FVIIIs and efanesoctocog alfa.MethodsThis phase 1 study (NCT05042440; EudraCT 2021-000228-37) enrolled previously treated adult men with severe hemophilia A. Patients received sequential single 50-IU/kg doses of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa after appropriate washout periods between each dose.ResultsThirteen participants were enrolled. Geometric mean elimination half-life of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa was 11.0, 15.4, and 43.3 hours, respectively, and area under the FVIII activity-time curve was 1670, 2820, and 10,100 IU × h/dL, respectively. Efanesoctocog alfa maintained mean FVIII activity levels of >40 IU/dL for up to 4 days and at ∼10 IU/dL on day 7. Corresponding times for >40 IU/dL and >10 IU/dL were <1 and <2 days, respectively, for octocog alfa and 1 day and 40 IU/dL) for up to 4 days after the dose and at ∼10 IU/dL on day 7.