Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection

TLDR

Telaprevir, a hepatitis C virus genotype‑1 protease inhibitor, has shown improved efficacy when combined with peginterferon‑ribavirin in phase 2 trials, suggesting it could shorten treatment duration. In a phase 3 randomized, double‑blind, placebo‑controlled trial of 1088 treatment‑naïve genotype‑1 HCV patients, telaprevir was added to peginterferon‑ribavirin for 12 or 8 weeks followed by standard therapy, compared with peginterferon‑ribavirin alone for 12 or 36 weeks. The combination achieved sustained virologic responses in 75% (T12PR) and 69% (T8PR) versus 44% with peginterferon‑ribavirin alone, with 58% of telaprevir patients completing only 24 weeks of therapy, but higher rates of anemia, gastrointestinal side effects, skin rashes, and a 10% discontinuation rate versus 7% in the control group. The study was funded by Vertex Pharmaceuticals and Tibotec (ClinicalTrials.gov NCT00627926).

Abstract

In phase 2 trials, telaprevir, a hepatitis C virus (HCV) genotype 1 protease inhibitor, in combination with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, has shown improved efficacy, with potential for shortening the duration of treatment in a majority of patients.In this international, phase 3, randomized, double-blind, placebo-controlled trial, we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups: a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks (T12PR group), followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks (T8PR group), followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria; or a group receiving placebo with peginterferon-ribavirin for 12 weeks, followed by 36 weeks of peginterferon-ribavirin (PR group). The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment (sustained virologic response).Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response (75% and 69%, respectively, vs. 44%; P<0.001 for the comparison of the T12PR or T8PR group with the PR group). A total of 58% of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment. Anemia, gastrointestinal side effects, and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone. The overall rate of discontinuation of the treatment regimen owing to adverse events was 10% in the T12PR and T8PR groups and 7% in the PR group.Telaprevir with peginterferon-ribavirin, as compared with peginterferon-ribavirin alone, was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment, with only 24 weeks of therapy administered in the majority of patients. (Funded by Vertex Pharmaceuticals and Tibotec; ADVANCE ClinicalTrials.gov number, NCT00627926.).