Non-Nucleoside HCV Polymerase Inhibitorchronic hepatitis C virus (HCV) infection

Setrobuvir - HCV

Direct-Acting Antiviral Being Developed for HCV

Setrobuvir (ANA598) is our direct-acting antiviral (DAA) currently in a Phase IIb study for the treatment of chronic hepatitis C virus (HCV) infection. Setrobuvir, which to date has shown potent antiviral activity and good safety, is a polymerase inhibitor that belongs to the chemical class of compounds known as non-nucleosides, which means that the compound requires no activation within the body prior to exerting its inhibitory effect, and does not resemble chemicals naturally found within the human body. In other viral diseases where non-nucleosides are used in therapy, these attributes of non-nucleosides have resulted in good safety parameters and minimal interference with the action of other drugs. Anadys retains all rights to setrobuvir, which was fully discovered at the Company.

Phase IIb Study

In January 2011, Anadys began dosing patients in a Phase IIb study evaluating setrobuvir in combination with pegylated interferon and ribavirin in both treatment-na´ve patients and patients who failed a prior course of HCV therapy with interferon and ribavirin. Approximately 275 patients are expected to be enrolled in the study and the study will be conducted at a number of sites within and outside of the United States. The primary endpoint of the study is Sustained Virological Response 24 weeks after patients complete treatment, known as SVR24.

We expect to receive antiviral data through 12 weeks for all patients, including the 8 week time point used for response-guided therapy in treatment-na´ve patients, in the third quarter of 2011. Antiviral response data through 24 weeks are expected in the fourth quarter of 2011.

Background to Phase IIb Study

Anadys laid the foundation for the current Phase IIb clinical trial with prior clinical and preclinical work. In a Phase IIa combination trial in HCV patients, we reported data that showed that setrobuvir added to pegylated interferon and ribavirin accelerated the rate of viral clearance, with comparable response at setrobuvir doses of 200 mg bid and 400 mg bid. A single patient out of more than 60 exhibited viral breakthrough while receiving setrobuvir plus standard of care, corresponding to a low breakthrough rate of < 2%. Setrobuvir also showed an excellent safety profile in the study through the 12 weeks of dosing, with reported adverse events being typical for patients treated with interferon and ribavirin alone, although conclusions regarding safety cannot be made until results in more patients over longer duration are known.

In a Phase I trial in HCV patients, setrobuvir demonstrated potent antiviral activity when dosed as monotherapy over three days. No patient at any dose level in the monotherapy study showed evidence of viral breakthrough while on setrobuvir, and there were no serious adverse events reported. Anadys has presented in vitro data supporting the use of setrobuvir in combination with interferon-alpha as well as several DAAs currently in development that act through diverse mechanisms. Data has shown that setrobuvir is synergistic in vitro with interferon-alpha as well as with representative HCV protease and polymerase inhibitors. In vitro combination treatment at clinically relevant concentrations of interferon-alpha and setrobuvir results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, setrobuvir retains full activity in vitro against mutations conferring resistance to protease inhibitors, nucleoside polymerase inhibitors and non-nucleoside polymerase inhibitors that act at binding sites distinct from that of setrobuvir, while protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to setrobuvir.

In 2009 Anadys completed long-term, chronic toxicology studies of setrobuvir, of 26 weeks duration in rats and 39 weeks duration in monkeys, and has reported favorable results that supported dosing for as long as a year in clinical studies.

Preclinical evaluation of setrobuvir was completed in the first quarter of 2008, leading to submission of an Investigational New Drug Application (IND) to the FDA, subsequent allowance of the IND by the FDA and initiation of clinical investigation in the second quarter of 2008.

Last Updated 6/1/2011
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