ANA598 - HCV
A Non-Nucleoside HCV Polymerase Inhibitor
ANA598 is our non-nucleoside polymerase inhibitor that we are developing for the treatment of chronic hepatitis C virus (HCV) infection. We are currently conducting a Phase II clinical trial of ANA598 in combination with pegylated interferon-alpha and ribavirin (standard of care or SOC) in which ANA598 is being dosed for 12 weeks at two doses levels: 200 mg given twice-daily (bid) and 400 mg given bid. The study is being managed by the Duke Clinical Research Institute (DCRI) under the leadership of John McHutchison, M.D. and is being conducted at a number of clinical sites in the United States.
ANA598 dosing is complete in the first dose cohort, 200 mg given bid, and Anadys expects to receive 12-week safety and antiviral response data for this cohort in the first quarter of 2010. Enrollment is complete in the second dose cohort, 400 mg given bid, and Anadys expects to receive 4-week safety and antiviral response at 400 mg bid at the end of the first quarter of 2010 and 12-week safety and antiviral response data in the second quarter of 2010.
In December 2009, Anadys reported positive preliminary antiviral response and safety results at week 4 from the first dose cohort (200 mg bid). In the group receiving ANA598 added to SOC, there was a steady increase in the percentage of patients with undetectable levels of virus from week 1 through week 4, with 56% of patients achieving undetectable levels of virus at week 4 (defined as Rapid Virological Response or RVR), compared to 20% of patients receiving placebo plus SOC achieving an RVR. No patient receiving ANA598 experienced viral rebound (defined as an increase in viral load of greater than 1 log10 from a prior measurement) through week 4. ANA598 also demonstrated a favorable safety profile through four weeks. There were no serious adverse events reported and the profile of adverse events reported was as expected for patients receiving SOC alone, with comparable rates observed between the ANA598 and placebo arms In the ongoing Phase II study, treatment-naïve genotype 1 patients are to receive ANA598 or placebo in combination with Pegasys® (peginterferon alfa-2a) and Copegus® (ribavirin, USP) for 12 weeks at dose levels of 200 mg or 400 mg both given twice daily (bid), each with a loading dose of 800 mg bid on day one. After week 12, patients are to continue receiving SOC alone. Patients who achieve undetectable levels of virus at weeks 4 and 12 will be randomized to stop all treatment at week 24 or 48. The primary endpoint of the study is the proportion of patients who achieve undetectable levels of virus at week 12 (defined as complete Early Virological Response, or cEVR). Additional endpoints include safety and tolerability as well as the proportion of patients with undetectable levels of virus at week 4 (defined as Rapid Virological Response, or RVR). Patients will be followed for 24 weeks after stopping therapy to determine the rate of Sustained Virological Response, or SVR. Approximately 90 patients are planned to be enrolled in this study - with approximately 30 patients receiving ANA598 and 15 receiving placebo at each dose level.
Anadys laid the foundation for the current Phase II clinical trial with prior clinical and preclinical work. In a Phase I trial in HCV patients, ANA598 demonstrated potent antiviral activity when dosed as monotherapy over three days. Anadys has presented in vitro data supporting the use of ANA598 in combination with interferon-alpha as well as with direct antivirals currently in development. Data has shown that ANA598 is synergistic in vitro with interferon-alpha as well as representative HCV protease and polymerase inhibitors. in vitro combination treatment at clinically relevant concentrations of interferon-alpha and ANA598 results in clearance of HCV RNA from cells rather than selection of resistant isolates. Furthermore, ANA598 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 ANA598, and protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
In September 2008, Anadys initiated long-term, chronic toxicology studies of ANA598, of 26 weeks duration in rats and 39 weeks duration in monkeys, and has reported favorable results. The completed toxicology studies support the ongoing Phase II clinical study as well as dosing ANA598 for as long as a year in future clinical studies.
Anadys retains full rights to ANA598, which was fully discovered at the Company. Preclinical evaluation of ANA598 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 1/27/2010
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ANA598 - HCV