Novel controlled-release Lemna-derived IFN-α2b (Locteron):: Pharmacokinetics, pharmacodynamics, and tolerability in a phase I clinical trial

Locteron (TM), a newly developed controlled-release formulation of Lemna-derived free (unpegylated) recombinant interferon-alpha 2b (IFN-alpha 2b, Biolex Therapeutics, Pittsboro, NC) in poly(ether-ester) microspheres (Poly-Active, OctoPlus N.V., Leiden, the Netherlands), was evaluated in 27 volunteers injected with either 20, 80, or 320 mu g Locteron (equivalent to 6.25, 25, or 100 X 10(6) IU, respectively), 80 mu g pegylated IFN-alpha 2b (PEG-IFN-alpha 2b), microspheres not containing IFN-alpha 2b, or placebo. Serum free or PEG-IFN-alpha 2b and two biomarkers of IFN activity, neopterin and 2',5'-oligoadenylate synthetase (2',5'-OAS), were measured. After injection of 320 mu g Locteron, serum IFN-alpha 2b remained elevated through 14 days. The elimination half-life of Locteron was more than 2-fold that of PEG-IFN-alpha 2b. The effects of 80 mu g Locteron and 80 mu g PEG-IFN-alpha 2b 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 mu g Locteron compared with 7 days after 80 mu g PEG-IFN-alpha 2b. Mild, moderate, or severe influenza-like symptoms developed in all 6 subjects receiving 80 1Ag PEG-IFN-alpha 2b. No such symptoms occurred after 20 or 80 mu g Locteron doses. Among the 4 recipients of 320 mu g 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.