Telaprevir Alone or with Peginterferon and Ribavirin Reduces HCV RNA in Patients with Chronic Genotype 2 but Not 3 Infections

Gastroenterology

Article in Press
 
Graham R. Foster, Christophe Hézode, Jean-Pierre Bronowicki, Giampiero Carosi, Ola Weiland, Lieselotte Verlinden, Rolf van Heeswijk, Ben van Baelen, Gaston Picchio, Maria Beumont

Received 8 December 2010; received in revised form 12 April 2011; accepted 16 May 2011. published online 01 June 2011.
Accepted Manuscript

Abstract

Background & Aims
We evaluated antiviral activity of 2 weeks therapy with telaprevir alone (T), peginterferon alfa-2a and ribavirin (PR), or all 3 drugs (TPR) in treatment-naïve patients with chronic hepatitis C virus (HCV) genotype (G) 2 or 3 infections.

Methods
We performed a randomized, multicenter, partially-blinded study of patients (23 with HCV G2, 26 with G3) who received telaprevir (750 mg every 8 hours) , placebo plus PR (Peg-IFN, 180 μg, once weekly and RBV, 400 mg, twice daily), or TPR for 15 days, followed by PR for 22 or 24 weeks. We quantified levels of HCV RNA in plasma.

Results
Levels of HCV RNA decreased in all patients with HCV G2, including those that received telaprevir monotherapy. The decrease was faster among patients that received telaprevir. By Day 15, 0 (telaprevir), 40% (TPR), and 22% (PR) of patients with HCV G2 had undetectable levels of HCV RNA; rates of sustained virologic response (SVR) were 56%, 100%, and 89%, respectively. Overall, 6/9 HCV G2 patients that received only telaprevir had viral breakthrough within 15 days. HCV RNA levels decreased slightly among patients with HCV G3 who received telaprevir, and decreased rapidly among patients given PR or TPR (telaprevir had no synergistic effects). SVR rates were 50%, 67%, and 44% among patients given telaprevir, TPR, or PR respectively; 7 patients with HCV G3 relapsed after therapy (2 given telaprevir, 3 given TPR, and 2 given PR) and 3 patients with HCV G3 had viral breakthrough during telaprevir monotherapy. The incidence of adverse events was similar among groups.

Conclusions
Telaprevir monotherapy reduces levels of HCV RNA in patients with chronic HCV G2 infections, but has limited activity in patients with HCV G3.

Keywords: C209, VX-950, liver disease, clinical trial

Source