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ANA598 Demonstrates Potent Antiviral Activity at all Dose Levels in Completed Phase Ib Study in Hepatitis C Patients
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Data Being Presented Today at 44th Annual Meeting of EASL
Management to Discuss Study Results and Program Status During Q1 Financial Results Call at 5 P.M. EDT Today
SAN DIEGO, April 23 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. (Nasdaq: ANDS) today announced that ANA598, the Company's investigational non-nucleoside polymerase inhibitor, demonstrated potent antiviral activity at all dose levels and was well tolerated in a Phase Ib study in which patients chronically infected with the Hepatitis C virus (HCV) were treated for three days. The results from the recently completed study are being presented today during the late-breaker poster session at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL) in Copenhagen, Denmark.
In the study, ANA598 treatment resulted in rapid and sustained reductions in HCV RNA with median reductions at end of treatment (Day 4) exceeding 2 log10 (>99%) at all dose levels. At 200 mg bid (twice-daily), the median viral load reduction was 2.4 log10 (range of 0.4 to 3.4); at 400 mg bid, 2.3 log10 (range of 1.6 to 3.5); and at 800 mg bid, 2.9 log10 (range of 2.2 to 3.4). Genotype 1a patients demonstrated median reductions of 1.4 log10, 1.8 log10, and 2.5 log10 at 200, 400 and 800 mg bid, respectively. In 10 of the 12 genotype 1a patients who received ANA598, viral load was still declining at the end of the three days of treatment. Genotype 1b patients demonstrated median reductions of 2.6 log10, 2.5 log10, and 3.2 log10, at 200, 400 and 800 mg bid, respectively. No patient showed evidence of viral rebound while on ANA598. ANA598 was well- tolerated in this short term study and there were no serious adverse events.
Steve Worland, Ph.D., Anadys' President and CEO, commented that "The potent antiviral activity demonstrated at all three doses in this study is very encouraging for the prospects of ANA598 when used in combination with other HCV agents. With the successful conclusion of this study in patients and the 14-day study in healthy volunteers, the positive 13-week animal toxicology results and ongoing manufacturing activities, the ANA598 program continues on track to be ready for Phase II in mid-2009."
The Phase Ib study was a randomized, double-blind, placebo-controlled, multiple ascending dose trial conducted to evaluate the safety, tolerability and antiviral activity of orally administered ANA598 in treatment-naive patients with chronic HCV genotype 1 infection. Patients were treated with ANA598 capsules (or matching placebo) at doses of 200 mg, 400 mg or 800 mg bid for three days. 35 patients participated in the study, with 11 receiving 200 mg bid, eight receiving 400 mg bid, eight receiving 800 mg bid and eight receiving placebo (with none of the patients receiving placebo showing an end of treatment response greater than 0.2 log10 reduction in viral load). Viral load at Day 4 (12 hours after the last dose) was compared to baseline HCV RNA levels.
"We're very pleased with the antiviral activity and safety of ANA598 in this study," commented James Freddo, M.D., Senior Vice President, Drug Development and Chief Medical Officer. "We believe the data continue to position ANA598 as a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV, and we look forward to investigating ANA598 in longer-term studies in combination with current standard of care."
ANA598 Program Update
Anadys continues to make progress on all aspects of the ANA598 program, including toxicology, manufacturing and a recently completed 14-day clinical study in healthy volunteers. The Company reiterates its expectation for the program to be ready mid-year for the first Phase II study of ANA598 in combination with pegylated interferon and ribavirin. The actual timing for the initiation of Phase II studies may depend on a number of factors, including FDA review timelines, the timing of any potential transaction around ANA598 or ANA773, available cash resources and funding activities, and the engagement of clinical sites.
14 Day Healthy Volunteer Study
Anadys recently completed dosing healthy volunteers in a 14-day study conducted to extend the safety and pharmacokinetic profile of ANA598. Thirty subjects participated in the study, with eight subjects receiving ANA598 and two subjects receiving placebo at each dose level (400 mg once-daily, 800 mg once-daily and 600 mg bid). Subjects received ANA598 or placebo on day one followed by pharmacokinetic assessment over days two and three and received subsequent doses consecutively on days four through fourteen. Preliminary results from the study indicate that ANA598 was generally well-tolerated in all cohorts with no serious adverse events, although three subjects receiving ANA598 (two in the 800 mg once-daily cohort and one in the 600 mg bid cohort) developed grade 2 rash and discontinued treatment after either six or seven days of consecutive dosing. There were no other instances of rash in this or any other st udy of ANA598. Data receipt and analysis from this study is continuing, and the Company expects to present the results at a clinical conference later this year. The Company believes the results of this study, combined with the results of the Phase Ib study in HCV patients, contribute to the attractive profile of ANA598 as an antiviral likely to be active in long-term studies in combination with pegylated interferon and ribavirin, and help position the program to be ready for Phase II in mid-2009.
Long-term Toxicology Studies
In September 2008, Anadys initiated long-term, chronic toxicology studies of ANA598, of 26 weeks duration in rats and 39 weeks duration in monkeys. Based on a now completed analysis of data at the 13-week interim in both species, the No Observed Adverse Effect Level (NOAEL) in monkeys and male rats remains 1000 mg/kg at 13 weeks, the highest dose being tested in the chronic studies. In female rats the NOAEL at the 13-week interim was 300 mg/kg, with the only adverse finding in female rats, observed only in the 1000 mg/kg dose group, being a marginal decrease in the rate of weight gain. Anadys previously reported NOAELs in both species after 28 days of 1000 mg/kg, the highest dose tested in that study. The dosing portion of the 26-week study in rats is now complete, while the dosing portion of the 39-week study in monkeys is scheduled to conclude in June. Anadys expects that the results from these chronic toxic ology studies, if continuing to be favorable, will enable dosing of ANA598 for up to 48 weeks in the Phase II study of ANA598 in combination with pegylated interferon and ribavirin.
ANA598 Preclinical Data at EASL Meeting
In addition to the results of the Phase Ib HCV patient study, Anadys is presenting additional data on the preclinical profile of ANA598 at the EASL Meeting at 4 p.m. CEST (7 a.m. PDT) on Friday, April 24. In an oral presentation, Anadys will present in vitro data showing that combinations of ANA598 with interferon-alpha, the protease inhibitor telaprevir and the nucleoside polymerase inhibitor PSI-6130 are synergistic. 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, through virtue of binding at a different site than ANA598, display a resistance profile distinct from that of ANA598. Genotypic mutations resistant to ANA598 will be shown to be fully susceptible to interferon-alpha, telaprevir and PSI-6130.
About ANA598
Anadys retains worldwide 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 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 December 2008, Anadys announced that the FDA granted fast track designation to ANA598 for the treatment of chronic HCV.
In October 2008, Anadys initiated patient dosing in the Phase Ib study of ANA598 in HCV patients and in February 2009 Anadys initiated dosing in a 14 day study in healthy volunteers.
In an earlier 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. All reported adverse events were classified as mild or moderate, with no apparent dose relationship. The pharmacokinetic profile demonstrated sustained plasma levels of ANA598 consistent with the potential for once-daily or twice-daily oral dosing.
In the preclinical program, ANA598 was well tolerated at all doses tested in 28-day GLP toxicology studies. In September 2008, Anadys initiated long-term, chronic toxicology studies of ANA598.
If ANA598 is successful in early stage development, the Company anticipates completion of the clinical, toxicology and manufacturing activities required to initiate Phase II studies of ANA598 in combination with current standard of care in mid-2009.
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 r eplication. 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 inducer of endogenous interferons that acts via the TLR7 pathway. 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 potency, safety and tolerability profile of ANA598, which may not be duplicated in future cohorts at higher doses or future clinical studies of longer duration; (ii) the belief that ANA598 is a leading non-nucleoside polymerase inhibitor in development for the treatment of HCV; (iii) the expectation that ANA598 will be active in long-term studies in combination with pegylated interferon and ribavirin and the ability to dose ANA598 for up to 48 weeks in future combination studies; (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 oth er 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 (including those described in this press release) 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, will maintain fast track designation 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 enter into transactions 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 cl inical 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. 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.
SOURCE Anadys Pharmaceuticals, Inc.
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