Clinical Medicine Reviews in Therapeutics

Current standard anti-HCV therapy with peginterferon/ribavirin is effective in only half of the patients and limited by side-effects that often necessitate discontinuation. Therefore, new treatments are being developed including specifically targeted antiviral therapy for HCV (STAT-C). Clinical development is most advanced for telaprevir, a HCV NS3/4A protease inhibitor. Phase 1 trials demonstrated potent antiviral effect but rapid emergence of resistance mutations which could be controlled by simultaneous administration of peginterferon. Phase 2 clinical trials (the PROVE trials) demonstrated superior efficacy of a telaprevir-based triple combination regimen for 24 weeks as compared to standard of care at an acceptable safety profile in chronic HCV genotype 1 infection both in the treatment-naïve (SVR 65% vs. 44%) and treatment-experienced (SVR 51% vs. 14%) setting. Phase 3 trials are currently ongoing in treatment-naïve as well as treatment-experienced HCV genotype 1 patients and SVR data are expected for the second half of 2010.