Intermune Announces Results of Actimmune Biomarker Study In Idiopathic Pulmonary Fibrosis
Monday May 19, 9:01 am ET
Diverse Mechanisms May Translate Into Beneficial Clinical Effects
SEATTLE, Wash. and BRISBANE, Calif., May 19 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN - News) announced today that a randomized, double-blind, placebo-controlled Phase II clinical trial of its lead product, Actimmune® (interferon gamma-1b) reveals important new clues regarding the multiple mechanisms through which the drug may exert its therapeutic effect in patients with idiopathic pulmonary fibrosis (IPF). The final results of the clinical trial were reviewed at the 99th International Conference of the American Thoracic Society (ATS) in Seattle.
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The goal of this exploratory Phase II trial was to gain further insight regarding the effects of interferon gamma-1b on the multiple molecular pathways believed to be involved in the pathogenesis of IPF, including fibroproliferation, angiogenesis, and antimicrobial defense.
"Interferon gamma-1b appears to downregulate molecules associated with fibrosis, inflammation, and angiogenesis, while upregulating molecules associated with anti-microbial defense, immunostimulation, and anti-angiogenesis," said Robert M. Strieter, M.D., Professor of Medicine and Pathology and Chief, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA. "A potentially important finding was the consistent and marked upregulation of i-TAC/CXCL11, a CXC chemokine with potent immunomodulatory, anti-microbial, and anti-angiogenic properties. This finding, in combination with the results of InterMune's recently reported Phase III trial, suggests that mortality in IPF may not be wholly attributable to a progressive loss of lung function, and that interferon gamma may improve survival through immunomodulatory and anti-angiogenic mechanisms."
Study Details
In the randomized, double blind, placebo-controlled Phase II clinical trial, 32 IPF patients received either 200 mg of interferon gamma-1b subcutaneously three times weekly or placebo for 6 to 12 months.
Endpoints in this exploratory study of biomarkers included the change from baseline in the level of mRNA transcription for TGF-beta and CTGF as the primary endpoint. Other endpoints included similar changes in several additional biomarkers, including profibrotic molecules, growth factors, cytokines, chemokines, and antimicrobial peptides.
A bronchoscopy was performed at baseline and 6 months for all study subjects. Bronchoalveolar lavage fluid, lung tissue, and plasma samples were collected to measure changes in transcription (mRNA) and translation (protein synthesis) of various biomarkers. Additionally, pulmonary function tests were performed at baseline and 6 months.
Interferon gamma-1b influenced a number of biomarkers that may be relevant in the pathogenesis of IPF. Specifically, interferon gamma-1b decreased the synthesis of profibrotic molecules (elastin, pro-collagen type III, platelet derived growth factor-B, IL-4) and proinflammatory and angiogenic molecules (ENA-78/CXCL5), while markedly increasing synthesis of i-TAC/CXCL11, a CXC chemokine with known immunomodulatory, anti-microbial, and anti-angiogenic properties. No significant difference was observed for the changes in mRNA transcription levels for TGF-beta and CTGF.
"The results of this study provide a plausible hypothesis for the mechanism of action of interferon gamma-1b and may provide an explanation for the previously observed survival benefit in patients with IPF," added Dr. Strieter.
About Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. Once symptoms appear, there is a relentless deterioration of pulmonary function and median survival of 2.8 years after diagnosis. There are currently no drugs approved by the FDA for the treatment of IPF. Approximately 75,000 patients suffer from this disease in the United States.
About Actimmune® (interferon gamma-1b)
Interferon gamma is a naturally occurring protein that stimulates the immune system. InterMune markets Actimmune® for the treatment of two life-threatening congenital diseases: chronic granulomatous disease and severe, malignant osteopetrosis. The most commons side effects are flu-like symptoms, including fever, headache and chills. InterMune is also conducting a Phase III study of interferon gamma-1b in ovarian cancer and a Phase II study of interferon gamma-1b for the treatment of severe liver fibrosis, or cirrhosis, caused by hepatitis C virus (HCV). Physicians and patients can obtain additional prescribing information regarding Actimmune®, including the product's safety profile, by visiting actimmune.com .
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