SAN DIEGO, Sept. 24 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. announced today preliminary results of a Phase I clinical trial of ANA598 in healthy volunteers and finalization of the protocol for a Phase Ib trial of ANA598 in patients chronically infected with hepatitis C virus (HCV). In the healthy volunteer study, ANA598 was well tolerated at all doses analyzed to date and no serious adverse events were reported. All doses achieved plasma drug concentrations predicted to display substantial antiviral activity based on preclinical results. The upcoming Phase Ib study of ANA598 in HCV patients will explore three dose levels -- 200 mg, 400 mg, and 800 mg, each taken twice daily (bid). ANA598 is the company’s investigational hepatitis C non-nucleoside polymerase inhibitor.
Phase I Study Results
In the Phase I study in healthy volunteers, ANA598 was administered as capsules at single doses starting at 400 mg. At the 2000 mg dose level, it was administered when fasted and also following a meal. In addition, a separate cohort received two 800 mg doses twelve hours apart. ANA598 was well tolerated at all doses analyzed to date and no serious adverse events were reported, 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. The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 with a half-life of more than 24 hours, consistent with the potential for once-daily or twice-daily oral dosing. All doses achieved plasma drug concentrations predicted to display substantial antiviral activity based on preclinical results. Additionally, absorption was enhanced when ANA598 was taken with food, indicating that it should not be necessary to take ANA598 on an empty stomach in order to achieve desired plasma drug levels.
Additional detail from the Phase I study, including full PK results from the twice-daily 800 mg cohort, will be presented at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), to be held in San Francisco, California, October 31 - November 4, 2008. Abstracts can be viewed at the AASLD website at http://www.aasld.org.
ANA598 Program Update
Anadys is now finalizing preparations to begin a Phase Ib trial of ANA598 in HCV patients early in the fourth quarter. The study will be conducted at several sites in the United States. The regulatory review necessary to initiate the study has been completed. In the Phase Ib monotherapy study, naive genotype 1 patients will receive ANA598 over three days, at doses of 200 mg bid, 400 mg bid or 800 mg bid. Ten patients are planned to be enrolled in each of the three cohorts, eight on active treatment and two on placebo. Anadys expects to have viral load data from all three cohorts in the first quarter of 2009. Anadys may elect to explore other dose levels of ANA598 and/or once-daily dosing in this study, depending on data from the first three cohorts.
In September, Anadys initiated long-term chronic toxicology studies of ANA598. As communicated in April of this year, Anadys made the strategic decision to accelerate into 2008 certain non-clinical activities for the ANA598 program, including the initiation of these long-term toxicology studies and the manufacture of additional drug substance. If ANA598 is successful in early stage clinical trials, it is anticipated that the acceleration of these non-clinical activities into 2008 will enable a more rapid and continuous development path into Phase II studies during 2009.
ANA598 Data to be Presented at AASLD Meeting
Anadys will present data on ANA598 during three poster sessions at the 59th Annual Meeting of the AASLD, to be held in San Francisco, California, October 31 - November 4, 2008. The full abstracts, which are summarized below, can be viewed at the AASLD website at http://www.aasld.org.
Anadys will present a late-breaker poster at a session beginning at 8:00 a.m. PST on Monday, November 3. The poster, titled “Results of a Phase I Safety, Tolerability and Pharmacokinetic Study of ANA598, a Non-Nucleoside NS5B Polymerase Inhibitor, in Healthy Volunteers”, will present data from the first clinical study of ANA598.
Two additional posters will be presented on Tuesday, November 4, 2008:
-- In a poster titled “Antiviral Efficacy of the HCV RNA Polymerase Inhibitor ANA598 in the Chimpanzee Model of HCV Infection”, Anadys will present data showing that ANA598 exhibits a substantial antiviral effect against both genotype 1a and 1b virus in HCV-infected chimpanzees. ANA598 was given as single and multiple oral doses and was well-tolerated in the study.
-- In a poster titled “In Vitro Studies Demonstrate that Combinations of Antiviral Agents that Include HCV Polymerase Inhibitor ANA598 have the Potential to Overcome Viral Resistance”, Anadys will present the results of in vitro studies that show ANA598 to be strongly synergistic with interferon-alpha. These studies also show that ANA598 retains activity against mutants known to confer resistance to other classes of direct antivirals, including protease inhibitors, nucleoside inhibitors and non-nucleosides that bind at the thumb site. In addition, genotypic mutations resistant to ANA598 will be presented and shown to be fully susceptible to interferon-alpha, a representative protease inhibitor and a representative nucleoside polymerase inhibitor.
About ANA598
Preclinical evaluation of ANA598 was completed in the first quarter of 2008, leading to submission of an Investigational New Drug Application (IND) to the U.S. Food and Drug Administration (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. Furthermore, ANA598 was shown to be active in a primate model of chronic HCV infection, leading to a greater than 2 log viral load decline in each of two genotype 1b infected animals. Anadys has previously reported data demonstrating that ANA598 retains undiminished activity against a number of HCV variants resistant to other direct antivirals currently in development.
Clinical Need and Market Opportunity in HCV Infection
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.
About Anadys
Anadys Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company dedicated to improving patient care by developing novel medicines in the areas of hepatitis C and oncology. For the treatment of chronic hepatitis C, the Company is developing two potentially complementary agents, ANA598, a non-nucleoside polymerase inhibitor and ANA773, an oral TLR7 agonist prodrug. The Company is also developing ANA773 for the treatment of cancer.
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) the expected timing and planned trial design of the ANA598 Phase Ib study, including Anadys’ expectation that it will have viral load data from all three cohorts in the first quarter of 2009; (ii) predictions of future antiviral activity based on plasma drug concentrations seen in the healthy volunteer study and preclinical results to date; (iii) the potential for once-daily or twice-daily oral dosing and the belief that it should not be necessary to take ANA598 on an empty stomach in order to achieve desired plasma drug levels; (iv) the ability of Anadys to transition into Phase II studies of ANA598 during 2009; and (v) expectations regarding the evolution of the market for HCV therapies. 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, will have favorable results in future clinical trials or will receive regulatory approval. 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 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 products, regulatory developments involving future products 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, 2007 and Anadys’ Form 10-Q for the quarter ended June 30, 2008. 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.
CONTACT: Investors, James T. Glover, SVP, Operations & CFO of Anadys
Pharmaceuticals, Inc., +1-858-530-3763, jglover@anadyspharma.com; or Media,
Ian Stone, ian.stone@russopartnersllc.com, or David Schull,
david.schull@russopartnersllc.com, both of Russo Partners, LLC,
+1-619-814-3510, for Anadys Pharmaceuticals, Inc.
Web site: http://www.anadyspharma.com/
http://www.aasld.org/
