Telaprevir: a hepatitis C NS3/4A protease inhibitor

Area of Science:

• Hepatology
• Virology
• Pharmacology

Background:

• Telaprevir is an FDA-approved NS3/4A protease inhibitor for chronic hepatitis C virus (HCV) genotype 1 infection.
• It is used in combination therapy to manage HCV genotype 1 infection.

Purpose of the Study:

• This article reviews published literature on telaprevir.
• The review covers its chemistry, mechanism of action, resistance, pharmacodynamics, pharmacokinetics, drug interactions, efficacy, and safety profile.

Main Methods:

• Searches of MEDLINE and BIOSIS databases (1975-January 2012) were conducted.
• Emphasis was placed on clinical trials, randomized controlled trials, and human research.
• Additional publications were identified through reference lists and scientific meeting abstracts.

Main Results:

• Telaprevir triple therapy significantly increased sustained virologic response (SVR) rates compared to standard dual therapy (peginterferon alfa and ribavirin [PR]).
• Phase III studies (ADVANCE, ILLUMINATE, REALIZE) demonstrated high SVR rates (up to 89%) with telaprevir-based regimens.
• Common adverse events included rash, pruritus, nausea, diarrhea, and anemia; drug interactions are a significant concern due to telaprevir's interaction with CYP3A4 and P-glycoprotein.

Conclusions:

• Telaprevir as part of triple therapy significantly increases the likelihood of achieving SVR in both treatment-naive and experienced patients with HCV genotype 1.
• The high cost of telaprevir may restrict its use to patient groups with poor response rates to dual therapy.