SAN DIEGO, Nov. 14 /PRNewswire-FirstCall/ -- Anadys Pharmaceuticals, Inc. announced today it will present results on the pharmacokinetics, pharmacodynamics, safety and tolerability of the isatoribine prodrug ANA975 in a Phase I clinical trial at a poster session on Monday, November 14, 2005 from 8:00 a.m.- 6:30 p.m. at the American Association of the Study of Liver Diseases (AASLD) Annual Meeting to be held at the Moscone Center in San Francisco, November 11-15, 2005.
ANA975 is an oral prodrug of isatoribine, a small molecule TLR7 agonist that has been administered intravenously to 68 subjects in clinical trials.
In this open-label, single-dose clinical trial conducted in the United Kingdom, 36 healthy volunteers each received a single, oral dose of ANA975 administered as a 5 mg/mL solution in the fasted state at doses of either 400 mg (n=6), 800 mg (n=18), or 1200 mg (n=12).
ANA975 was well tolerated at all doses investigated in the trial, with no serious adverse events. However, 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.
ANA975 was rapidly and extensively converted to isatoribine, with maximum concentration (Cmax) of isatoribine typically occurring within one hour after dosing. At the highest tested dose, which has an isatoribine dose content of 988 mg, plasma isatoribine area-under-the-curve (AUC) values (range 23-40, median 27 mg*h/L) were similar to those observed in a previously reported clinical proof-of-concept study of once daily intravenous (IV) infusions of 800 mg of isatoribine (first dose AUC range 19-38, median 24 mg*h/L). The similarity of AUC values at comparable molar doses of oral ANA975 and IV isatoribine indicates that oral absorption and conversion of ANA975 were very high.
“These data are encouraging and support further clinical studies of ANA975 as an investigational agent for oral therapy of chronic hepatitis C virus,” said Brad Kerr, Ph.D., Anadys’ Vice President, Clinical Affairs.
In the prior proof-of-concept clinical study, IV infusion of 800 mg of isatoribine once a day for seven days to patients chronically infected with hepatitis C virus (HCV) yielded a significant reduction of plasma HCV RNA that correlated with induction of 2', 5'- oligoadenylate synthetase (OAS). The poster at AASLD will also present results on OAS induction over longer time periods in animals. Oral administration of ANA975 to cynomolgus monkeys for 28 days resulted in sustained induction of OAS over the dosing interval. OAS levels returned to baseline after cessation of dosing. These encouraging results indicate that it is possible to maintain a sustained activation of the immune system, for at least 28 days, through stimulation of TLR7. Longer-term studies in humans will be required to determine the ultimate benefit to HCV patients of TLR7 stimulation.
Anadys is developing ANA975 in collaboration with Novartis for chronic hepatitis C virus (HCV) as well as potentially other infectious disease indications.
These clinical findings and additional preclinical correlations observed for isatoribine and its oral prodrug ANA975 will be discussed at the poster presentation on November 14, 2005 at 8:00 a.m. The abstract, entitled “Pharmacokinetics, Safety and Tolerability of the Isatoribine Oral Prodrug ANA975 in a Phase I Healthy Volunteers Study,” is now available on the AASLD website at www.aasld.org.
About Anadys
Anadys Pharmaceuticals, Inc. is a biopharmaceutical company committed to advancing patient care by discovering, developing and commercializing novel small molecule medicines for the treatment of hepatitis C virus (HCV), hepatitis B virus (HBV) and other serious infections. The Company has core expertise in Toll-Like Receptor-based small molecule therapeutics and structure-based drug design coupled with medicinal chemistry. Anadys’ clinical development programs include ANA975 for the treatment of HCV and HBV, and ANA380 for the treatment of HBV. In addition, Anadys’ therapeutic platform is designed to advance a strong and continual pipeline of drug candidates into the clinic.
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 the safety and tolerability profile of ANA975, the extent to which ANA975 is converted to isatoribine and the corresponding oral bioavailability of ANA975, the potential for ANA975 to be an oral therapy for chronic hepatitis C virus, as well as references to the reduction of plasma HCV RNA and the correlation with the induction of OAS seen in early-stage clinical trials of isatoribine and whether it is possible to maintain a sustained activation of the immune system in humans through stimulation of TLR7. 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. In particular, the results of initial clinical trials may not be predictive of future results, and Anadys cannot provide any assurances that any of its product candidates will have favorable results in future clinical trials or receive regulatory approval. In addition, Anadys’ results may be affected by risks related to the implementation of its collaboration with Novartis, competition from other biotechnology and pharmaceutical companies, its effectiveness at managing its financial resources, its ability to successfully develop and market products, the level of effort that its collaborative partners devote to development and commercialization of its product candidates, difficulties or delays in its 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. These and other factors that may cause actual results to differ are more fully discussed in the “Risk Factors” section of Anadys’ Form 10-Q for the quarter ended September 30, 2005. 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.
Anadys Pharmaceuticals, Inc.
CONTACT: Vince Reardon, Sr. Director, Investor Relations & CorporateCommunications of Anadys Pharmaceuticals, Inc., +1-858-530-3653,vreardon@anadyspharma.com
Web site: http://www.aasld.org//
