SAN DIEGO, Sept. 9 Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) announced today that dosing has begun in a Phase II trial of ANA598 in patients chronically infected with hepatitis C virus (HCV). The study will evaluate ANA598 over 12 weeks, taken in combination with pegylated interferon-alpha and ribavirin, in treatment naive HCV patients. ANA598 is an investigational, oral, non-nucleoside polymerase inhibitor.
"ANA598 has demonstrated potent antiviral activity and good tolerability as a single agent, as well as preclinical properties indicative of likely synergy when used clinically in combination regimens," said James Freddo, M.D., Anadys' Senior Vice President, Drug Development and Chief Medical Officer. "We look forward to building upon these results to demonstrate the benefit of ANA598 when used in combination with interferon and ribavirin."
About the Phase II Study
In the Phase II study, naive genotype 1 patients will receive ANA598 or placebo in combination with Pegasys((R)) (peginterferon alfa-2a) and Copegus((R)) (ribavirin, USP) (a current standard of care, or SOC) for 12 weeks at dose levels of 200 mg or 400 mg twice daily (bid), each with a loading dose of 800 mg bid on day one. After week 12, patients will continue to receive SOC. 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 with undetectable 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 virus at week 4 (defined as Rapid Virological Response, or RVR), weeks 24 and 48, and 24 weeks after stopping all treatment (defined as Sustained Virological Response, or SVR).
Ninety patients are planned to be enrolled in this study -- thirty patients receiving ANA598 and fifteen receiving placebo at each dose level. The study will be managed by the Duke Clinical Research Institute (DCRI) under the leadership of John McHutchison, M.D. and will be conducted at a number of clinical sites in the United States.
Anadys expects to receive 28-day safety and response (RVR) data from the 200 mg dose level by year-end and additional on-treatment safety and response data from both cohorts during the first two quarters of 2010.
ANA598 is a non-nucleoside inhibitor of the HCV RNA polymerase. Anadys has completed three Phase I clinical studies of ANA598 that have demonstrated potent antiviral activity and good tolerability. In a monotherapy study in naive genotype 1 patients, treatment with ANA598 for three days led to median declines in viral load ranging from 2.4 to 2.9 log10 in three separate dose groups. No patient at any dose level showed evidence of viral rebound while on ANA598, and there were no serious adverse events.
Anadys has completed dosing in two long-term chronic toxicology studies of ANA598 (26 weeks duration in rats and 39 weeks duration in monkeys). At the 13-week interim, the toxicology profile of ANA598 in both species was very favorable. A preliminary assessment of the results from the 26-week study in rats indicates a similar profile to that seen in rats at 13 weeks, in which the only adverse finding was a marginal decrease in the rate of weight gain in females at 1000 mg/kg, the highest dose tested. Complete results from both studies, including 39-week data from the monkey study, are expected at the end of the third quarter 2009.
Anadys has presented results from multiple in vitro studies that support the clinical use of ANA598 in combination with interferon-alpha. In particular, data have shown that ANA598 is synergistic in vitro with interferon-alpha, that mutations conferring resistance to ANA598 remain fully sensitive to interferon-alpha, and that synergy between ANA598 and interferon-alpha is retained against mutations conferring resistance to ANA598. Anadys has also presented in vitro results supporting future clinical combination studies with direct antivirals, including a demonstration of in vitro synergy between ANA598 and representative HCV protease and polymerase inhibitors. Furthermore, Anadys has presented data that show 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 that protease and nucleoside polymerase inhibitors retain full activity in vitro against mutations conferring resistance to ANA598.
ANA598 has received Fast Track Status from the FDA for the treatment of chronic hepatitis C.
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to improving patient care by developing novel medicines for the treatment of hepatitis C. The Company believes hepatitis C represents a large unmet medical need in which meaningful improvements in treatment outcomes may be attainable with the introduction of new medicines. The Company is developing ANA598, a non-nucleoside polymerase inhibitor for the treatment of hepatitis C. The Company has also investigated the potential of ANA773, an oral, small-molecule inducer of endogenous interferons that acts via the Toll-like receptor 7, or TLR7, pathway in hepatitis C.
Safe Harbor Statement
Statements in this press release that are not strictly historical in nature constitute "forward-looking statements." Such statements include, but are not limited to, references to (i) Anadys' expectation that the Phase II study will build upon prior results of ANA598 studies and demonstrate a benefit when ANA598 is used in combination with interferon and ribavirin; (ii) the ability for patients in the ANA598 Phase II study to achieve undetectable levels of virus at weeks 4 and 12 and to achieve SVR; (iii) Anadys' expectation that it will receive 28-day data from the 200 mg dose level by year end and additional data during the first two quarters of 2010; (iv) the antiviral and tolerability profile of ANA598 seen to date, which may not be duplicated in the Phase II study; and (v) preclinical properties indicative of likely synergy when used clinically in combination regimens and in vitro studies which Anadys believes support the clinical use of ANA598 in combination with interferon-alpha and future combination studies of ANA598 with direct antivirals. Such forward-looking statements involve known and unknown risks, uncertainties and other factors, which may cause Anadys' actual results to be materially different from historical results or from any results expressed or implied by such forward-looking statements. For example, the results of preclinical and early clinical studies may not be predictive of future results, and Anadys cannot provide any assurances that ANA598 will not have unforeseen safety issues or will have favorable results in the Phase II trial. In addition, Anadys' results may be affected by risks related to competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to enter into collaborations around its product candidates, its ability to successfully develop and market products, difficulties or delays in its preclinical studies or clinical trials, difficulties or delays in manufacturing its clinical trials materials, the scope and validity of patent protection for its product candidates, regulatory developments involving its product candidates and its ability to obtain additional funding to support its operations. Risk factors that may cause actual results to differ are more fully discussed in Anadys' SEC filings, including Anadys' Form 10-K for the year ended December 31, 2008 and Anadys' Form 10-Q for the quarter ended June 30, 2009. All forward-looking statements are qualified in their entirety by this cautionary statement. Anadys is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.
Pegasys(R) and Copegus(R) are registered trademarks of Hoffman-La Roche Inc.
SOURCE Anadys Pharmaceuticals, Inc.