Anadys Pharmaceuticals Commences Dosing in Phase II Study of ANA598

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Anadys Pharmaceuticals Commences Dosing in Phase II Study of ANA598

Wed Sep 9, 2009 7:30am EDT

ANA598 To Be Dosed for 12 Weeks in Triple Combination

SAN DIEGO, Sept. 9 /PRNewswire-FirstCall/ -- 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 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(®) (peginterferon alfa-2a) and

Copegus(®) (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 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. About ANA598

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.