BOSTON, Oct. 30 /PRNewswire-FirstCall/ -- InterMune, Inc. announced today the presentation of preclinical research describing the synergistic antiviral activity of ITMN-191, its orally-available hepatitis C virus (HCV) NS3/4A protease inhibitor, in combination with PEG-Interferon alfa-2a (PEG-IFN alfa-2a, Pegasys(R)). These in vitro findings were presented at the American Association for the Study of Liver Diseases (AASLD) 57th annual meeting in Boston, Massachusetts.
The antiviral activity of the combination of ITMN-191 and PEG-IFN alfa-2a was evaluated in vitro in two replicon systems, the HCV genotype-1b and a derivative with reduced sensitivity to ITMN-191. Peak synergy was seen at predicted therapeutically relevant concentrations of each drug and was of greater magnitude than that observed for other experimental HCV protease inhibitors currently in development. In addition, PEG-IFN alfa-2a greatly improved ITMN-191 potency in both replicon systems, and the variant with reduced sensitivity to ITMN-191 demonstrated hypersensitivity to PEG-IFN alfa- 2a, suggesting that the combination of ITMN-191 and PEG-IFN alfa 2a, may exert combined antiviral effects that increase the barrier for the development of drug resistant variants.
“Our continued research designed to better understand the antiviral effects of ITMN-191, alone and in combination with PEG-IFN alfa-2a, provides important insight into the potential for novel treatment paradigms that will be explored further in clinical studies of ITMN-191,” said Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune. “We anticipate that future therapeutic approaches to the treatment of chronic hepatitis C will involve multiple agents, likely in combination with interferon, and we are hopeful that these combinations will lead to improved, sustained virologic responses for patients who are in need of more optimal therapies.”
Additionally, Scott Seiwert, Ph.D., Vice President of Discovery Research at InterMune, presented research at the 1st International Workshop on Hepatitis C - Resistance and New Compounds. The presentation detailed the selection of variants of the HCV replicon with reduced sensitivity to ITMN- 191. This research demonstrates that amino acid substitutions at position 168 of the HCV serine protease play an important role in reducing sensitivity of the HCV replicon to ITMN-191. While important, however, single substitutions at position 168 are not sufficient to confer resistant at concentrations that correlated to estimates of liver exposure following oral dosing of ITMN-191. Rather, substitution at multiple sites is required to confer resistance to ITMN-191, suggesting that the genetic barrier to resistance in patients following clinical dosing of ITMN-191 may be relatively high.
About ITMN-191
InterMune has successfully completed preclinical toxicology and pharmacokinetic studies in multiple species in support of initiating Phase I clinical studies of ITMN-191 for the treatment of chronic HCV. The European Clinical Trial Authorization (CTA) application, which InterMune filed in the third quarter of 2006, includes results of 28-day preclinical toxicology studies utilizing doses many-fold higher than those expected to be given to humans. These studies demonstrate that ITMN-191 has a favorable toxicology profile, allowing the compound to be studied in clinical trials over a range of doses predicted to have antiviral efficacy. ITMN-191 has also demonstrated high in vitro potency and specificity in biochemical assays and in assays utilizing the HCV replicon system. Moreover, ITMN-191 displays a favorable cross-resistance profile, including significant potency against variants of the NS3/4A protease that are resistant to other HCV protease inhibitors currently in development. Preclinical pharmacokinetic results support the exploration of twice-daily oral dosing in HCV patients. On October 16, 2006, InterMune signed a collaboration agreement with Roche for the research, development and commercialization of ITMN-191 and potential second-generation HCV protease inhibitor compounds.
About HCV and HCV Protease Inhibitors
According to the Centers for Disease Control and Prevention (CDC), an estimated 3.9 million Americans (1.8%) have been infected with HCV, of whom 2.7 million are chronically infected. According to the World Health Organization (WHO), it is estimated that there are 170 million people worldwide afflicted with this disease. Currently available therapies are insufficient, creating a need for the development of novel therapeutic approaches. The HCV NS3/4 protease is an attractive drug target because of its potential involvement in viral replication and suppressive effects on host response to viral infection. Inhibitors of the HCV protease, such as ITMN-191, represent a promising new class of drugs for HCV.
About InterMune
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes two Phase III programs evaluating possible therapeutic candidates for treatment of patients with IPF. The INSPIRE trial is evaluating Actimmune(R) and the CAPACITY program is evaluating pirfenidone. The hepatology portfolio includes ITMN-191, the lead HCV protease inhibitor compound, a second- generation HCV protease inhibitor program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.
Except for the historical information contained herein, this press release contains certain forward-looking statements that involve risks and uncertainties, including without limitation the statements related to the progress, future patient enrollment in and timing of our clinical trials and announcements of results thereof. All forward-looking statements and other information included in this press release are based on information available to InterMune as of the date hereof, and InterMune assumes no obligation to update any such forward-looking statements or information. InterMune’s actual results could differ materially from those described in InterMune’s forward- looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those discussed in detail under the heading “Risk Factors” in InterMune’s annual report on Form 10-K filed with the SEC on March 13, 2006 (the “Form 10-K”) and updates included in the most recent Form 10-Q filed with the SEC on August 8, 2006 (the “Form 10-Q”), and other periodic reports filed with the SEC, including the following: (i) risks related to the development of our product and product candidates; (ii) risks related to timely patient enrollment and retention in clinical trials, including the use of third parties to conduct such clinical trials; (iii) risks related to achieving positive clinical trial results; (iv) risks related to our intellectual property rights; and (v) risks related to the uncertain, lengthy and expensive clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues. The risks and other factors discussed above should be considered only in connection with the fully discussed risks and other factors discussed in detail in the Form 10-K and InterMune’s other periodic reports filed with the SEC.
InterMune, Inc.
CONTACT: investors, Investor Relations Dept of InterMune, Inc.,+1-415-466-2242, or ir@intermune.com, or media, Pam Lord of Porter NovelliLife Sciences, +1-619-849-6003, or plord@pnlifesciences.com, for InterMune
Web site: http://www.intermune.com/
