Anadys Pharmaceuticals receives fast track for ANA598 treatment of chronic hepatitis C virus

Dec 1 2008

Anadys Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted fast track designation to ANA598 for the treatment of chronic hepatitis C virus (HCV) infection. ANA598 is Anadys' investigational hepatitis C non-nucleoside polymerase inhibitor.

Anadys is currently enrolling patients in a Phase Ib study evaluating ANA598 for the treatment of patients chronically infected with HCV.

Under the FDA Modernization Act of 1997, fast track designation is designed to facilitate the development and expedite the review of new drugs that are intended to treat serious or life-threatening conditions. Compounds selected must demonstrate the potential to address an unmet medical need for such a condition. Mechanisms intended to facilitate development include opportunities for frequent dialogue with FDA reviewers and for timely review of submitted protocols. However, the designation does not guarantee approval or expedited approval of any application for the product. The granting of fast track status for the ANA598 development program is consistent with the need for HCV treatments with novel mechanisms of action, oral administration, non-overlapping resistance profiles and improved safety and efficacy over the existing standard of care for both treatment-naive and treatment-experienced patients.

"The FDA's fast track designation for ANA598 acknowledges the need for new HCV therapies to improve treatment outcomes," commented James Freddo, M.D., Anadys' Senior Vice President, Drug Development and Chief Medical Officer. "We anticipate continuing to work closely with the FDA on the development and regulatory review of ANA598, one of the few non-nucleoside polymerase inhibitors in clinical development for the treatment of HCV. We continue to believe this class of antivirals holds great promise as a component of future HCV treatment regimens."

Anadys recently initiated patient dosing in a Phase Ib study of ANA598 in HCV patients. In the Phase Ib study, naive genotype 1a and 1b patients are to receive ANA598 over three days at doses of 200 mg bid (twice-a-day), 400 mg bid or 800 mg bid. Ten patients will be enrolled at each dose level, eight receiving active drug and two receiving placebo.

In a Phase I study in healthy volunteers, ANA598 was administered as capsules at single oral doses of 400 mg, 800 mg, 1400 mg, 2000 mg (fed and fasted) and 3000 mg. In addition, a separate cohort received two 800 mg doses 12 hours apart. ANA598 was well tolerated at all doses and there were no serious adverse events or withdrawals from the study, although definitive conclusions regarding product safety and tolerability cannot be made until the results of future clinical trials of longer duration in more patients are known. All reported adverse events were classified as mild or moderate, with no apparent dose relationship. The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 with a half-life of 24 to 30 hours in the fasted state and 22 hours in the fed state, consistent with the potential for once-daily or twice-daily oral dosing.

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. In the preclinical program, ANA598 was well tolerated at all doses tested in 28-day GLP toxicology studies. In September, Anadys initiated long-term, chronic toxicology studies of ANA598. If ANA598 is successful in early stage clinical trials, it is anticipated that the acceleration of these and other non-clinical activities into 2008 will enable a more rapid and continuous development path into Phase II studies during 2009.

Chronic HCV infection is a serious public health concern affecting approximately 3.2 million people in the United States and approximately 170 million people worldwide. HCV causes inflammation of the liver, which can lead to fibrosis and cirrhosis, and may ultimately lead to liver failure and/or liver cancer if not successfully treated. Cirrhosis of the liver resulting from chronic HCV infection is the leading indication for liver transplantation in the U.S. Due to the asymptomatic nature of HCV infection, it often goes undetected for up to 20 years following initial infection. Each year, 8,000 to 10,000 people in the U.S. die from complications of HCV.

The current standard of care is a combination of pegylated interferon and ribavirin. Inadequate response rates, in particular for patients infected with genotype 1 HCV, along with significant side effects of approved therapy, support the medical need for improved treatment options. It is estimated that fewer than 5% of people with chronic HCV infection living in the U.S. are under treatment today. Most infected individuals are unaware of their infection status and the large majority of individuals who know their condition do not currently receive drug therapy. There is also a growing number of individuals who have failed interferon-based regimens who may be successfully treated with combinations of two or more direct antivirals. It is expected that the next generation of therapies for treatment of HCV will include small molecules, such as ANA598, that directly act upon specific viral enzymes to inhibit viral replication. These new therapies are expected to improve overall therapy by increasing cure rates and potentially improving tolerability and convenience of treatment if doses of currently used agents can be reduced or eliminated.