InterMune Presents Research on ITMN-191 in Hepatitis C at EASL Annual MeetingPresentations include preclinical data for potential combination therapies and details of N3/4A protease sequence variations after ITMN-191 exposure
BARCELONA, Spain, April 11, 2007 /PRNewswire-FirstCall/ -- InterMune, Inc. announced today the presentation of findings from three in vitro experiments concerning its HCV protease inhibitor ITMN-191, alone or in combination with other compounds, at the 42nd Annual Meeting of the European Association for the Study of the Liver in Barcelona, Spain.
The first presentation concerned the activity of ITMN-191 alone or in combination with PEG-IFN-alfa-2a (Roche's Pegasys(R)) in an in vitro model of HCV clearance. These experiments explored the concentrations of ITMN-191 needed to achieve HCV replicon clearance from a human liver cell line during a two-week course of treatment. Complete clearance of replicon RNA was achieved with a 14-day treatment of only 45 nM of ITMN-191; a concentration well below that achieved in the liver of animal species following twice-daily oral dosing. Combination of the minimum human plasma concentration of PEG-IFN-alfa-2a with 15 nM of ITMN-191 also promoted durable replicon clearance, indicating clinical investigation of the anti-HCV activity of the two agents in combination is warranted.
The second experiment described the synergistic antiviral activity of ITMN-191 with Roche's R1479, an inhibitor of the HCV NS5B polymerase. The in vitro antiviral activity of each agent was enhanced when used in combination. Additionally, the replicon with reduced sensitivity to ITMN-191 remained fully sensitive to R1479, suggesting that the combination of these two agents could decrease the potential for the development of drug-resistant HCV variants in monotherapy treatments.
"With our continued research, we are better understanding the antiviral effects of ITMN-191, alone and in combination with other agents, such as polymerase inhibitors and interferons, and discovering important insights into possible treatment regimens for chronic hepatitis C," said Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune. "We anticipate that treatment regimens will involve multiple agents, and we are hopeful that these combinations will lead to improved, sustained virologic responses for patients who are in need of more optimal therapies."
The third presentation concerned NS3 sequence variations in HCV replicons after exposure to ITMN-191 at clinically relevant concentrations. The NS3 sequence was found to undergo dynamic changes when exposed to increasing concentrations of ITMN-191. As was seen in previous work, substitution at position 168 of NS3 appears to be fundamental to resistance but alone is not sufficient for HCV replicon persistence at all ITMN-191 concentrations achieved in the liver of animal species following oral dosing. This suggests that the genetic barrier to resistance in patients following clinical dosing of ITMN-191 may be significant dependent upon human liver exposure.
InterMune currently is conducting a Phase 1a clinical study of ITMN-191 for the treatment of chronic HCV. Preclinical toxicology and pharmacokinetic studies in multiple species demonstrated that ITMN-191 has a favorable toxicology profile, significant liver exposure, high in vitro potency and specificity, and an advantageous cross-resistance profile, including considerable effectiveness against variants of the NS3/4A protease that are resistant to other HCV protease inhibitors currently in development. The preclinical pharmacokinetic results support the exploration of twice-daily oral dosing. InterMune and Roche have a collaboration agreement for the research, development and commercialization of ITMN-191 (referred to as R7227 within the Roche research and development programs) and second-generation HCV protease inhibitor compounds.
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. It is estimated that there are 170 million people worldwide afflicted with this disease. While currently available therapies can cure many patients, there is considerable 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.
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 the Phase 3 program, CAPACITY, which is evaluating pirfenidone as a possible therapeutic candidate for the treatment of patients with IPF and a research program focused on small molecules for pulmonary disease. The hepatology portfolio includes the HCV protease inhibitor compound ITMN-191 in Phase 1a, 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 30, 2007 (the "Form 10-K") and updates included in the most recent Form 10-Q filed with the SEC on November 7, 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.
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Web site: http://www.intermune.com/
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Posted: April 2007