Anadys Pharmaceuticals Announces Single Dose Safety and Pharmacokinetics Results for ANA598 in Healthy Volunteers
Phase I Clinical Data and Additional Preclinical Results for Non-Nucleoside HCV Polymerase Inhibitor Being Presented at AASLD
SAN DIEGO, November 01, 2008 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. announced today the results of a Phase I clinical trial of ANA598 in healthy volunteers and additional preclinical data that support ANA598 as one of the leading non-nucleoside polymerase inhibitors currently in development for the treatment of HCV. These results are being presented at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) being held in San Francisco, California, from October 31 - November 4. ANA598 is the Company's investigational hepatitis C non- nucleoside polymerase inhibitor.
ANA598 Phase I Study Results
In the 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 and no pattern of events within any body system. 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. In the cohort that received two 800 mg doses 12 hours apart, the concentration of ANA598 in plasma 12 hours after the second dose was 83 ug/mL, which substantially exceeds the level predicted to display antiviral potency. The data will be presented in a late-breaker poster titled "Results of a Phase I Safety, Tolerability and Pharmacokinetic Study of ANA598, a Non-Nucleoside NS5B Polymerase Inhibitor, in Healthy Volunteers", at 1:00 p.m. PST on Monday, November 3.
ANA598 Preclinical Data at AASLD Meeting
In addition to the results of the Phase I healthy volunteer study, Anadys is presenting additional data on the preclinical profile of ANA598 at the AASLD Meeting on Tuesday, November 4.
-- 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 synergistic with interferon-alpha, the protease inhibitor telaprevir (VX-950), and the nucleoside polymerase inhibitor PSI-6130 (the active agent of R7128). 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. Genotypic mutations resistant to ANA598 will be shown to be fully susceptible to interferon-alpha, telaprevir (VX-950) and PSI-6130. Data will also be presented demonstrating synergy between ANA598 and cytokines induced by ANA773, Anadys' TLR7 agonist oral prodrug, also in development for hepatitis C. These data strongly support the potential for ANA598 to be used in combination with multiple other agents approved or under investigation for hepatitis C.
-- 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. In two HCV genotype 1b animals dosed over four days, maximum viral load reductions of 2.2 and 2.6 log10 were observed within 24 to 48 hours after the initial dose. In one animal the viral load reduction was sustained throughout the remaining dosing period, while in the second animal a modest rise in viral load was seen over days three and four. In two HCV genotype 1a animals that each received a single dose of ANA598, viral load reductions of 0.5 and 1.4 log10 were seen at 48 hours post-dose.
Anadys recently initiated patient dosing in a Phase Ib study of ANA598 in HCV patients. Naive genotype 1a and 1b patients will 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. Anadys recently completed dosing in the Phase I study of ANA598 in healthy volunteers.
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. 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.
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.
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 belief that ANA598 is one of the leading non-nucleoside polymerase inhibitors currently in development for the treatment of HCV; (ii) the potential for ANA598 to be used in combination with multiple other agents approved or under investigation for hepatitis C; (iii) the potential for once-daily or twice-daily oral dosing of ANA598; (iv) the level of plasma drug concentration of ANA598 predicted to display antiviral potency; (v) the ability of Anadys to transition into Phase II studies of ANA598 during 2009; and (vi) 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 and ANA773 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 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, 2007 and Anadys' Form 10-Q for the quarter ended September 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.
Posted: November 2008