12 High Svr12 With 16 Weeks of Tegobuvir and Gs-9256 With Peginterferon-Alfa 2a and Ribavirin in Treatment-Naive Genotype 1 HCV Patients

Development and application of a fast, reproducible assay to measure HCV NS3 protease activity using Escherichia coli lysate

“…We then tested NS3 protease double mutants. The GT1a double mutant R155K + D168G and the GT1b double mutants V36M + A156T and V36M + R155K were previously observed in a GS-9256 multiple ascending dose study (Lawitz et al, 2010;Mo et al, 2012;Nelson et al, 2012;Zeuzem et al, 2012). Analysis of these mutants in a replicon system was not possible due to poor replication.…”

Preclinical Characterization of the Novel HCV NS3 Protease Inhibitor GS-9256

“…Since the development of the first generation NS3 protease inhibitors (telaprevir, boceprevir), several new NS3 protease inhibitors with better tolerability, lower drugdrug interaction potential and improved resistance profiles have been approved or are under clinical development. GS-9256 is a selective inhibitor of GT1 NS3 protease with potent antiviral activity demonstrated in Phase I and Phase II clinical studies [10][11][12][13]. Here, the preclinical properties of GS-9256 including in vitro antiviral activity, cross-resistance and pharmacokinetic properties in non-human species are described.…”

“…In a 28-day Phase IIa study, the combination of GS-9256, tegobuvir (GS-9190), PEG-IFN and ribavirin demonstrated 100% rapid virological response and a safety and tolerability profile comparable to PEG-IFN and ribavirin (RBV) alone [12]. In a Phase IIb study, 95% (40/42) of patients treated with GS-9256 in combination with tegobuvir, PEG-IFN and RBV achieved SVR12 [13]. In this report, we communicate the in vitro properties of GS-9256, including in vitro potency, cross-resistance and activity combined with other classes of HCV inhibitors as well as its in vitro and in vivo metabolic and pharmacokinetic properties.…”

New therapeutic strategies in HCV: polymerase inhibitors

“…Rapid viral response was observed in 100% (14 of 14) of patients receiving tegobuvir/GS‐9256/PEG‐IFN/RBV . Response‐guided quadruple therapy with tegobuvir and GS‐9256 plus PEG‐IFN/RBV based on a virological response at week 2 enabled to shorten antiviral therapy to 16 weeks and yielded an SVR rate of 95% .…”