Table 5

 Current status of hepatitis C virus (HCV) enzyme inhibitor development (April/2006)

Stage of development
Large phase II trials in combination with pegylated interferon (PEG-IFN) with or without ribavirin have started. The combination of PEG-IFN may be necessary to prevent drug resistance. More HCV enzyme inhibitors are in development (for example, GS-9132, Gilead, Achillion; ITMN-191, Intermune; JTK-002/3, Japan Tobacco; HCV-796, ViroPharma, Wyeth; BILB-1941, Boehringer Ingelheim).
HCV protease inhibitors
    BILN-2061 (Boehringer Ingelheim)Phase I (2–3 log10 decline in HCV-RNA after 2 days). More effective in HCV genotype 1 than 3 patients.96,104Program halted
    VX-950 (Vertex)Phase I monotherapy (4.4 log10 decline in HCV-RNA after 14 days),97 in combination with PEG-IFN. 5.5 log decline in HCV-RNA after 14 days.111 Phase IIb studies have been initiated (prove 1 and 2).
    SCH503034 (Schering-Plough)Phase I monotherapy (2.06 log10 decline of HCV-RNA after 14 days), stronger antiviral effect in combination with PEG-IFN.98,99 Phase IIb trial started
HCV polymerase inhibitors
    NM-283, Valopicitabine (Idenix)Phase I (∼1 log decline after 14 days), phase II (NM-283 plus PEG-IFN stronger effect compared with PEG-IFN plus ribavirin after 12 weeks therapy).100,101,112 However, 800 mg dose group was stopped due to gastrointestinal symptoms. Studies are ongoing with 200–400 mg NM-283.112
    R1626 (Roche)Phase I (1.2 log decline in HCV-RNA after 14 days with 1500 mg bid).113