Copyright ©2007 Baishideng Publishing Group Inc.
World J Gastroenterol. Nov 21, 2007; 13(43): 5673-5681
Published online Nov 21, 2007. doi: 10.3748/wjg.v13.i43.5673
Table 1 Anti-HCV agents currently under clinical development
CompoundClinical advancement ntViral efficacyResistance (HCV resistant variants)Remarks
Protease inhibitorsTelaprevirII(dose-750 mg q8h; genotype-1)Low level: V36A/M, T54A, R155K/T, A156SRash, GI and hematological adverse events (AE)
(VX-950)PROVE- 1, 2, 3VLR = 3 log d 3High level: A156V/T, V36A/M-R155K/T, V36A/M-A156V/T;
VLR = 4.4 log: d 14After 14 d of treatment
VLR = 5.5 log: d 14 when combined with PEG-IFNa2a
SCH 503034II(dose 400 mg q8h; genotype-1)Low to moderate levels:Frequency of AE comparable to control group receiving placebo
VLR = 2.06 log d 14V170A
VLR = 2.9 log: when combined with PEG-IFNT54A
High level: A156T
Inhibitor of protease cofactor NS4AACH-806I/IIVLR = 1 log: d 5Single mutation at N-terminus of NS3; lack of cross resistance to any of the polymerase inhibitors or protease inhibitors now under developmentReversible nephrotoxicity
Polymerase inhibitorsValopicitabine (NM283)IIVLR = 0.8 log: d 28S282TGI and hematological AE
VLR = 2.7 log: d 28, when combined with PEG-IFN
VLR = 4.24 log: wk 24, when combined with PEG-IFN
R1479 (R1626)IIVLR = 3.7 log for 4500 mg q12h at d 14, VLR = 2.6 log for 3000 mg q12hno dataMild to moderate hematological AE with increasing doses
HCV-796IIVLR = 1.4-1.5 log: d 4C316YMild to moderate headache-the most frequent AE; no treatment-emergent serious AE
VLR = 3.3-3.5 log: d 14, when combined with PEG-IFN
BILB 1941IData incomplete due to high discontinuation rateNo dataGI AE
Cyclophilin inhibitorsDEBIO 025IVLR = 3.6 log: d 14 of monotherapyNo breakthrough during the treatmentTransitional hyperbilirubinemia