Aliment Pharmacol Ther 2011; 34: 443-453 Summary Background The ANA773 is an oral prodrug of a small-molecule toll-like receptor (TLR)7 agonist. Preclinical and healthy volunteer clinical studies with ANA773 have demonstrated induction of endogenous interferon-α (IFN-α) of multiple subtypes, which supports the potential utility in the treatment of chronic hepatitis C virus (HCV) infection. Aim To examine safety, tolerability, pharmacodynamics, pharmacokinetics and anti-viral activity of ANA773. Methods The ANA773 was investigated in a double-blind, placebo-controlled study in 34 patients chronically infected with HCV of any genotype. Patients were treatment-naïve or had relapsed following previous interferon-based treatment. This dose escalation study was composed of four dose groups (800, 1200, 1600 and 2000 mg). In each group, six to eight patients received ANA773 and two received placebo. Patients were dosed with ANA773 every-other-day for either 28 days (800, 1200 or 1600 mg) or 10 days (2000 mg). Results Mild to moderate adverse events were reported, with an increase in frequency and intensity with increasing dose. No serious AEs were reported and there were no early discontinuations. There were dose-related increases in various markers of IFN-α response. The mean maximum change in serum HCV RNA level from baseline was -0.34, -0.29, -0.40, -0.97 and -1.26 log10in the placebo, 800, 1200, 1600 and 2000 mg cohorts, respectively. At the 2000 mg dose, ANA773 significantly (P = 0.037) reduced serum HCV RNA levels (range: 0.14 to -3.10 log10). Conclusion The ANA773 was generally well tolerated and resulted in a dose-related IFN-dependent response leading to a significant decrease in serum HCV RNA levels in the 2000 mg dose group.,
Alimentary Pharmacology and Therapeutics
Erasmus MC: University Medical Center Rotterdam

Bergmann, J., Bruijne, J., Hotho, D., de Knegt, R., Boonstra, A., Weegink, C., … Reesink, H. (2011). Randomised clinical trial: Anti-viral activity of ANA773, an oral inducer of endogenous interferons acting via TLR7, in chronic HCV. Alimentary Pharmacology and Therapeutics, 34(4), 443–453. doi:10.1111/j.1365-2036.2011.04745.x