MONTREAL, Nov. 1 /PRNewswire-FirstCall/ -- InterMune, Inc. announced today the presentation of in vitro studies examining the biological activity of Actimmune(R) (interferon gamma-1b), currently in Phase III trials, and pirfenidone, a second late stage candidate for treatment of patients with idiopathic pulmonary fibrosis (IPF). The findings were presented orally at CHEST, the 71st Annual Meeting of the American College of Chest Physicians being held in Montreal this week.
“Data presented by our researchers at CHEST provide important insight to the potential anti-fibrotic and anti-inflammatory activity of our two Phase III compounds for IPF, which is characterized by inflammation and fibrosis of the lungs,” stated Lawrence M. Blatt, Ph.D., InterMune’s Senior Vice President of Research. “Our deeper understanding of the molecular pathways affected by our compounds allows us to theorize what the clinical effects may be in patients with treatment, such as potentially improved lung function and slower disease progression.”
Interferon Gamma-1b Inhibits Interleukin-4, Endothelin-1, and Transforming Growth Factor-Beta-Induced Up-regulation of Type I Collagen in Cellular Models of Lung Fibrosis
Using an in vitro model of lung fibrosis, this study demonstrated that Actimmune(R) may reduce fibrosis through multiple pathways. Three pro-fibrotic cytokines believed to play a role in IPF -- interleukin-4, endothelin-1, and transforming growth factor-beta -- were each used to signal collagen synthesis in human lung cells. Actimmune(R) was effective at reducing collagen synthesis, a key step in fibrosis, through all three signal mechanisms. Some other drugs in development for IPF only target a single pathway, such as the endothelin-1 fibrotic pathway.
Pirfenidone Mediates Differential Effects on Lipopolysaccharide-Induced Cytokine Expression in Human Peripheral Blood Mononuclear Cells
This study is the first to explore the mechanism of pirfenidone’s anti-inflammatory activity in freshly isolated human cells. Activating white blood cells with pathogenic signals causes the production of several inflammatory cytokines, which will trigger an immune response. Pre-treating these cells in vitro with pirfenidone modulated the production of these cytokines, measured by a multiplex cytokine assay. Pirfenidone exerted an overall anti-inflammatory effect through multiple mechanisms. Specifically, pirfenidone decreased white blood cell production of tumor necrosis factor-beta and interleukin-1-beta, which each signal production of the pro-fibrotic cytokine transforming growth factor-beta. At the same time, pirfenidone increased production of interleukin-10, which attenuates the fibrotic response.
About IPF
IPF is a disabling and ultimately fatal disease that affects approximately 83,000 people in the United States, with an estimated 35,000 new cases developing each year. Those diagnosed with IPF are usually between the ages of 50 and 70, and the disease tends to affect men more than women. IPF causes inflammation and scarring (fibrosis) in the lungs, hindering a person’s ability to process oxygen and causing shortness of breath (dyspnea) and cough. IPF is a progressive disease, meaning that over time, lung scarring and symptoms increase in severity. Median survival time from diagnosis is three to five years in patients with IPF. There are currently no drugs approved by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMEA) for the treatment of IPF.
About Actimmune(R)
Interferon gamma is a naturally occurring protein that stimulates the immune system. InterMune markets Actimmune(R) for the treatment of two life-threatening congenital diseases: chronic granulomatous disease and severe, malignant osteopetrosis. The most common side effects are flu-like symptoms, including headache, fatigue, fever, chills, and rash. InterMune is conducting two late-stage trials of Actimmune(R): the INSPIRE Trial, a Phase III study of interferon gamma-1b in IPF, and the GRACES Trial, a Phase III study of interferon gamma-1b in ovarian cancer. InterMune was recently granted two composition of matter patents related to interferon gamma-1b in the United States, extending its patent protection until 2022. Physicians and patients can obtain additional prescribing information regarding Actimmune(R), including the product’s safety profile, by visiting www.actimmune.com.
About pirfenidone
Pirfenidone is an orally active, small molecule that shows a wide range of biologic activity. In vitro evidence has shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Data presented from four Phase II clinical trials in over 250 patients suggest that pirfenidone may impact lung function and disease progression in patients with IPF. In these clinical studies, pirfenidone was generally well tolerated with the most frequent side effects reported being nausea, photosensitivity rash, fatigue, cold syndrome, and gastrointestinal symptoms. In 2004, the FDA and EMEA granted pirfenidone orphan drug designation for the treatment of IPF. InterMune has worldwide rights, excluding Japan, Korea and Taiwan, to develop and commercialize pirfenidone for all fibrotic diseases. InterMune anticipates initiating a Phase III program evaluating pirfenidone in IPF in the first half of 2006.
About InterMune
InterMune is a biopharmaceutical company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a broad and deep late-stage product portfolio addressing IPF and hepatitis C virus (HCV) infections, particularly nonresponders, or those patients who do not respond to first-line therapy. The pulmonology portfolio includes Actimmune(R) and pirfenidone. Actimmune(R) is being evaluated in the INSPIRE Trial, a Phase III study in patients with IPF. Pirfenidone is also being developed for the treatment of IPF. In addition to three-times-a-week Infergen(R) (interferon alfacon-1), a currently marketed product indicated for the treatment of chronic HCV infections, the hepatology portfolio includes the DIRECT Trial, a Phase III study of daily Infergen(R) plus ribavirin in non-responders. Additionally, InterMune is developing a pre-clinical stage small molecule program targeted at the HCV protease. For additional information about InterMune and its development 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 product development. 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 quarterly report on Form 10-Q filed with the SEC on August 9, 2005 (the “Form 10-Q”) and other periodic reports filed with the SEC, including the following: (i) risks related to the development of our products and product candidates; (ii) risks related to government regulation and approval of our products and product candidates; (iii) risks related to whether InterMune is able to obtain, maintain and enforce patents and other intellectual property; (iv) risks related to the uncertain, lengthy and expensive clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues; (v) risks related to achieving positive clinical trial results; and (vi) 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-Q and InterMune’s other periodic reports filed with the SEC.
InterMune, Inc.
CONTACT: investors, Judy Hayes of InterMune, Inc., +1-415-466-2242, orir@intermune.com; or media, Pam Lord of Atkins + Associates,+1-858-527-3494, or plord@irpr.com, for InterMune, Inc.
Web site: http://www.intermune.com/
