Novel Controlled-Release Lemna -Derived IFN- α 2b (Locteron): Pharmacokinetics,Pharmacodynamics,and Tolerability in a Phase I Clinical Trial

Abstract

Locteron^™, a newly developed controlled-release formulation of Lemna-derived free (unpegylated) recombinant interferon-α2b (IFN-α2b, Biolex Therapeutics, Pittsboro, NC) in poly(ether-ester) microspheres (PolyActive, OctoPlus N.V., Leiden, the Netherlands), was evaluated in 27 volunteers injected with either 20, 80, or 320 μg Locteron (equivalent to 6.25, 25, or 100 × 10₆ IU, respectively), 80 μg pegylated IFN-α2b (PEG-IFN-α2b), microspheres not containing IFN-α2b, or placebo. Serum free or PEG-IFN-α2b and two biomarkers of IFN activity, neopterin and 2′,5′-oligoadenylate synthetase (2′,5′-OAS), were measured. After injection of 320 μg Locteron, serum IFN-α2b remained elevated through 14 days. The elimination half-life of Locteron was more than 2-fold that of PEG-IFN-α2b. The effects of 80 μg Locteron and 80 μg PEG-IFN-α2b on both neopterin and 2′,5′-OAS were in a comparable range. Serum persistence of both these biomarkers was similar at 14 days after 320 μg Locteron compared with 7 days after 80 μg PEG-IFN-α2b. Mild, moderate, or severe influenza-like symptoms developed in all 6 subjects receiving 80 μg PEG-IFN-α2b. No such symptoms occurred after 20 or 80 μg Locteron doses. Among the 4 recipients of 320 μg Locteron, 1 experienced mild and 2 experienced moderate influenza-like symptoms. Locteron merits further clinical investigation as a hepatitis C therapy suitable for dosing once per 2 weeks.