Donald M. Jensen, Tarik Asselah, Douglas Dieterich, Graham R. Foster, Mark S. Sulkowski, Stefan Zeuzem, Parvez Mantry, Eric M. Yoshida, Christophe Moreno, Denis Ouzan, Mark Wright, Luis E. Morano, Robert Buynak, Marc Bourlière, Tarek Hassanein, Shuhei Nishiguchi, Jia-Horng Kao, Masao Omata, Seung W. Paik, David K. Wong, Edward Tam, Kelly Kaita, S. Victor Feinman, Jerry O. Stern, Joseph Scherer, Anne-Marie Quinson, Florian Voss, John-Paul Gallivan, Wulf O. Böcher, Peter Ferenci
Introduction & aim. Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. Material and methods. Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24?48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). Results. SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17?31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16?30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. Conclusion. Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.
Key words. Hepatitis C, Viral hepatitis, Direct-acting antiviral, SVR12