Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3

Background & Aims To examine the antiviral activity of boceprevir, a hepatitis C virus (HCV) protease inhibitor, in HCV genotype (G) 2/3-infected patients. Methods We assessed boceprevir and telaprevir activity against an HCV G2 and G3 isolates enzyme panel, in replicon, and in phenotypic cell-based assays. Additionally, a phase I study evaluated the antiviral activity of boceprevir monotherapy (200mg BID, 400mg BID, or 400mg TID) vs . placebo for 14days in HCV G2/3 treatment-naive patients. Results Boceprevir and telaprevir similarly inhibited G1 and G2 NS3/4A enzymes and replication in G1 and G2 replicon and cell-based assays. However, telaprevir demonstrated lower potency than boceprevir against HCV G3a enzyme ( K i =75nM vs. 17nM), in the G3a replicon assay (EC 50 =953nM vs. 159nM), and against HCV G3a NS3 isolates (IC 50 =3312nM vs. 803nM) in the cell-based assay. In HCV G2/3-infected patients, boceprevir (400mg TID) resulted in a maximum mean decrease in HCV RNA of −1.60log vs. −0.21log with placebo. Conclusions In vitro , boceprevir is more active than telaprevir against the HCV G3 NS3/4A enzyme in cell-based and biochemical assays and against G3 isolates in replicon assays. In HCV G2/3-infected treatment-naive patients, decreases in HCV RNA levels with boceprevir (400mg TID) were comparable to those observed with the same dose in HCV treatment-experienced G1-infected patients.