- Results of Phase 1 clinical studies support advancement to Phase 2 - - Results of in-vitro study of ITMN-191 with Roche polymerase inhibitors -
BRISBANE, Calif., Sept. 24 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) today announced that four abstracts from clinical and in-vitro studies of ITMN-191 (R7227) accepted for presentation at the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD, Oct. 31 - Nov. 4 in San Francisco), may now be viewed at http://www.aasld.org. ITMN-191 is a hepatitis C virus (HCV) NS3 protease inhibitor, currently in a Phase 1b clinical trial in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin). The compound is being developed in collaboration with Roche.
Dan Welch, Chairman, Chief Executive Officer and President of InterMune, said, "Collectively, these abstracts demonstrate that in the experiments conducted, ITMN-191 was safe and very well tolerated in humans and demonstrated viral kinetics that are competitive with other direct anti-viral compounds in development. The safety and viral kinetic profile of ITMN-191 was observed in mono-therapy regimens administered twice-a-day and three-times-a-day in both treatment-naive patients and in patients who had failed to adequately respond to standard-of-care treatment. Additionally, results from in-vitro experiments of the antiviral effect of ITMN-191 in combination with two separate HCV polymerase inhibitors in the Roche portfolio suggest the potential benefit of treatment regimens that simultaneously target the HCV protease and polymerase."
Results of Two Clinical Studies of ITMN-191
-- A Phase 1a Single-Ascending-Dose (SAD) Study in Healthy Volunteers (Poster #1871): ITMN-191 was safe and well tolerated when given as a single dose to healthy adults in a range of doses from 2mg to 1600mg. Adverse events were generally mild and transient and were similar between treatment groups, with the exception of a higher frequency of mild and transient diarrhea and abdominal pain in the ITMN-191 group at the highest tested dose (1600mg). The pharmacokinetics of ITMN-191 were linear over the dose range of 100mg to 800mg. Co-administration of ITMN-191 with food increased the expected trough and AUC by 40-50% compared with administration of ITMN-191 without food. This "food effect" enabled InterMune and Roche to explore a lower range of doses of ITMN-191 in subsequent clinical studies than was previously planned.
-- A Phase 1b Monotherapy Multiple-Ascending-Dose (MAD) Study in HCV Genotype 1 Patients (Poster #1847): ITMN-191 was administered as mono-therapy for 14 days to four cohorts of treatment-naive patients infected with HCV genotype 1. Multiple ascending doses were examined up to a total daily dose of 600mg. The safety and tolerability of ITMN-191 were excellent. Adverse events were generally mild and transient, with no evidence of clinically significant laboratory abnormalities or ECG changes. When ITMN-191 was administered every eight or twelve hours, viral kinetic results were very competitive with those of other direct antiviral compounds studied in similar experiments.
The MAD study also included one exploratory cohort of ITMN-191 given as mono-therapy for 14 days to strictly defined non-responders: HCV genotype 1 patients who had failed to achieve a 2.0 log10 reduction in HCV RNA with prior standard-of-care treatment, or who still had detectable HCV RNA after 24 weeks of treatment. At the one dose studied of 300mg given every 12 hours, ITMN-191 delivered a median reduction of HCV RNA at study day 14 of 2.5 log10. The results from this initial exploratory cohort in non-responders encouraged InterMune and Roche to continue their plans to aggressively study ITMN-191 in this difficult to treat population and provided an important insight to the range of doses to explore in future studies.
-- Pharmacokinetic (pk) and Pharmacodynamic (pd) Results in the Phase 1b MAD Study (Poster #1861): ITMN-191 was intentionally designed to achieve a high liver-to-plasma ratio in HCV patients in order to reduce any potential side effects associated with systemic circulation of drug. Poster #1861 shows that the strong viral kinetic results reported in abstract #1847 were associated with very low plasma concentrations, achieving the key objective of a high liver-to-plasma ratio in patients infected with HCV. The pharmacokinetics of ITMN-191 in mono-therapy were more than dose proportional at higher doses.
Results of In Vitro Combinations of ITMN-191 plus direct anti-virals in HCV models
-- Two Experiments of the Combination of ITMN-191 with HCV Polymerase Inhibitors R7128 and R1626 (Poster #1885): ITMN-191 was combined separately with two polymerase inhibitors, R7128 (Roche/Pharmasset) and R1626 (Roche) in two assays. One assay modeled HCV replication (14-day replicon clearance assay) and the other assay modeled viral resistance (a 3-week colony formation assay model). The combination of ITMN-191 with the active moeity of either R7128 or R1626 resulted in significantly enhanced clearance of the HCV replicon and reduced or suppressed the emergence of drug-resistant viral variants.
This work was carried out in anticipation of future clinical studies using ITMN-191 with either R7128 or R1626, and demonstrates that such combinations would likely result in significantly greater antiviral activity than has been observed with any of these agents in previous monotherapy trials.
Current Development of ITMN-191
Based on the encouraging results reported in the above studies, in late May 2008 InterMune initiated an ongoing 14-day study of ITMN-191 in combination with Pegasys(R) (peginterferon alfa-2a) and Copegus(R) (ribavirin). The study is exploring doses of ITMN-191 that were studied in mono-therapy (up to 600mg daily) and is also exploring higher doses. The study is meeting the companies' expectations. Top-line results from the triple combination study are anticipated to be released in the fourth quarter of 2008.
InterMune's ITMN-191 Presentations at AASLD
Titles of the InterMune posters to be presented at AASLD regarding the ITMN-191 development program are as follows:
Poster #1871: A Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Single Ascending Oral Doses of the NS3/4A Protease Inhibitor ITMN-191 in Healthy Subjects
Poster #1847: Treatment of Chronic Hepatitis C Virus (HCV) Genotype 1 Patients with the NS3/4A Protease Inhibitor ITMN-191 Leads to Rapid Reductions in Plasma HCV RNA: Results of a Phase 1b Multiple Ascending Dose (MAD) Study
Poster #1861: Pharmacokinetic-Pharmacodynamic (PK-PD) Relationships for ITMN-191 in a Phase 1 Multiple Ascending Dose (MAD) Trial in Patients with Genotype 1 Chronic Hepatitis C (CHC) Infection
Poster #1885: Combination of the NS3/4A Protease Inhibitor ITMN-191 (R7227) with the Active Moiety of the NS5B Inhibitors R1626 or R7128 Enhances Replicon Clearance and Reduces the Emergence of Drug Resistant Variants
The American Association for the Study of Liver Diseases (AASLD) is the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease. AASLD fosters research that leads to improved treatment options for millions of liver disease patients. The organization advances the science and practice of hepatology through educational conferences, training programs, professional publications, and partnerships with government agencies and sister societies.
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 (referred to as R7227 at Roche) in Phase 1b, a second-generation HCV protease inhibitor research program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit http://www.intermune.com.
This news release contains forward-looking statements within the meaning of section 21E of the Securities Exchange Act of 1934, as amended, that reflect InterMune's judgment and involve risks and uncertainties as of the date of this release, including without limitation the statements related to anticipated product development timelines. 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 most recent annual report on Form 10-K filed with the SEC on March 14, 2008 (the "Form 10-K") and other periodic reports filed with the SEC, including the following: (i) risks related to the long, expensive and uncertain clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues or delays in anticipated timing of the regulatory approval process; (ii) risks related to failure to achieve the clinical trial results required to commercialize our product candidates; and (iii) risks related to timely patient enrollment and retention in clinical trials. 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, all of which are available via InterMune's web site at http://www.intermune.com.
Pegasys(R) and Copegus(R) are registered trademarks of Roche.
|SOURCE InterMune, Inc.|
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