Conference Reports for NATAP

EASL 43rd Annual Meeting of the European Association For The Study Of The Liver Milan, Italy April 23-27, 2008 Back

POTENT ANTIVIRAL ACTIVITY OF THE HCV NUCLEOSIDE POLYMERASE INHIBITOR, R7128, IN COMBINATION WITH PEG-IFN a-2a AND RIBAVIRIN       Reported by Jules Levin 43rd Annual Meeting of EASL, Milan, Italy, April 23-27, 2008   J. Lalezari, E. Gane, M. Rodriguez-Torres, E. DeJesus, D. Nelson, G. Everson, I. Jacobson, R. Reddy, G.Z. Hill, A. Beard, W.T. Symonds, M.M. Berrey, and J.G. McHutchison   AUTHOR CONCLUSIONS   Significant antiviral effect of R7128 in combination with PEG-IFN alpha-2a and RBV over 4 weeks   -- 85% patients with undetectable HCV RNA by week 4 (R7128 1500 mg BID + PEG-IFN_-2a/RBV)   -- 5.1 log10 mean decrease in HCV RNA   R7128 safe and well tolerated over the 4 weeks: -- no substantial differences from expected events observed with PEG-IFN_-2a/RBV -- No hematologic or other toxicity identified   R7128: Next steps   Two additional cohorts will be enrolled in the current 4-week triple combination study -- R7128 1000 mg BID + PEG-IFN_-2a/RBV in GT-1a/b Rx-naive -- R7128 1500 mg BID + PEG-IFN_-2a/RBV in GT-2/3 prior non-responders   International phase 2b study to evaluate R7128 in triple combination for up to 12 weeks -- R7128 at doses of 1000 and 1500 mg BID -- PEG-IFN_-2a and RBV   R7128: Specific Nucleoside Polymerase Inhibitor of HCV   R7128 is a prodrug of PSI-6130 and PSI-6206   Mode of action via chain termination   Completed single ascending oral dose studies in healthy volunteers for PSI-6130 and R7128   Completed 14-day multiple ascending oral dose study in HCV patients who failed interferon -- 2.7 log10 (>99%) Mean HCV RNA decrease with 1500mg twice-daily (BID) dose1 -- No maximum tolerated dose identified -- No evidence of viral resistance detected to date2   Study Objectives and Design   Objective -- Evaluate safety/tolerability, antiviral activity and viral resistance   Design -- Multi-center, randomized, double-blind (R7128) -- 4-week combination with peginterferon _-2a (PEGASYS)+ RBV (COPEGUS) with follow-up safety data on SOC to day 56 -- Patient population Treatment-naive, genotype 1 Non cirrhotic (Metavir ≦ 2, Knodell ≦ 3, Ishak ≦ 4)   --HCV RNA Assay: COBAS AmpliPrep/COBAS TaqMan HCV Test, RUO Version (lower limit of detection 15 IU/mL) -- Samples for HCV NS5B resistance testing collected before, during and after the treatment period.