Antiviral activity of danoprevir (ITMN-191/RG7227) in combination with pegylated interferon α-2a and ribavirin in patients with hepatitis C

Abstract

Background. Current therapy options for patients with chronic hepatitis C virus (HCV) infection genotype 1 are effective in <50%. Danoprevir (ITMN-191/RG7227) is a potent, selective, and orally active inhibitor of the HCV NS3/4A serine protease. Methods. The safety and antiviral efficacy of danoprevir was examined over 14 days in combination with pegylated interferon α-2a (180 μg once weekly) and ribavirin (1000-1200 mg/day) in a double-blind, placebo-controlled, phase 1b, multiple ascending dose study consisting of 6 dose cohorts (400 mg, 600 mg, and 900 mg twice daily and 100 mg, 200 mg, and 300 mg 3 times daily). Results. Danoprevir in combination with pegylated interferon α-2a and ribavirin was safe and generally well tolerated. The median change in HCV RNA level from baseline to the end of treatment with danoprevir at 400 mg, 600 mg, and 900 mg twice daily was -4.7 log10 IU/mL, -5.4 log10 IU/mL, and -5.3 log10 IU/mL, respectively, and at 100 mg, 200 mg, and 300 mg 3 times daily was -5.5 log10 IU/mL, -5.7 log10 IU/mL, and -5.6 log10 IU/mL, respectively. Placebo administered in combination with standard of care resulted in median decrease in HCV RNA level of -2.6 log10 IU/mL (with twice daily regimen) and -2.0 log10 IU/mL (with 3 times daily regimen). Conclusions. Our study showed substantial antiviral efficacy of danoprevir in combination with pegylated interferon α-2a and ribavirin. Exploration of the safety and antiviral efficacy of danoprevir in longer clinical studies is warranted. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.