InterMune Inc has completed patient randomization of its large Phase II clinical trial of Actimmune (Interferon gamma-1b) injection for the treatment of severe liver fibrosis, or cirrhosis, caused by hepatitis C virus (HCV). The objective of the study, called AEGIS (Anti-fibrotic Efficacy Gamma Interferon Study), is to evaluate the safety and anti-fibrotic activity of Actimmune in HCV patients who have failed standard antiviral therapy.

"We commend the dedicated efforts of clinical investigators and their staff for the rapid completion of randomization of this trial," said Henry Hsu, Vice President of Clinical Research at InterMune. "Preclinical and preliminary clinical data suggest that interferon gamma may prevent or reverse the development of cirrhosis. Based on these data, we believe the results of this trial, which we expect in mid-2004, could represent a major advance in the management of patients with advanced liver disease."

In this Phase II, multi-center, placebo-controlled study, 500 patients with severe liver fibrosis or early cirrhosis associated with hepatitis C infections were randomized to receive either placebo, 100 mcg of Actimmune or 200 mcg of Actimmune three times per week via subcutaneous injection. The study is designed to evaluate the proportion of patients showing a reduction of one or more points on the fibrosis staging score (using the Ishak histology staging system, a commonly used measure in this disease) following treatment with Actimmune, compared to placebo.

More than four million people are affected with HCV in the United States, and current antiviral therapy for HCV infection is effective in only approximately 50% of patients. Because treatment is often not effective, continued HCV infection leads to severe liver fibrosis or cirrhosis (scarring caused by the accumulation of tough fibrous proteins). These patients are at an increased risk of developing life-threatening complications such as internal bleeding, inability to remove toxins from the blood, progressive liver failure and death.

"There is a clear and very large unmet medical need in patients suffering from HCV-related liver fibrosis," said Scott Harkonen, President and Chief Executive Officer of InterMune. "Actimmune is a promising therapy against this disease, and if demonstrated safe and effective in this study, could also possibly be used broadly to treat other forms of liver cirrhosis such as those caused by alcoholism, metabolic disorders or the hepatitis B virus. This represents what we believe to be a significant new, potentially multi-billion dollar market opportunity for Actimmune."

Actimmune is being investigated as a potential treatment for liver fibrosis based on an emerging body of evidence that demonstrates the importance of interferon gamma as a cytokine that modulates the interaction of a downstream protein, transforming growth factor-beta (TGF-beta), that has been shown to play a critical role in the pathogenesis of fibrotic diseases. Data from in vitro studies, studies in animal models of liver fibrosis and studies in humans with HCV infections suggest a potential therapeutic role for interferon gamma in the inhibition of fibrosis in the liver and other organs.

Actimmune is the recombinant form of interferon gamma-1b, a naturally occurring protein that stimulates the immune system. InterMune currently markets Actimmune for the treatment of two rare congenital diseases, chronic granulomatous disease (CGD) and severe, malignant osteopetrosis. The company is also conducting or planning to conduct multiple Phase II and Phase III clinical studies with Actimmune for the potential treatment of a variety of diseases, including idiopathic pulmonary fibrosis, cryptococcal meningitis, ovarian cancer, non-Hodgkin's lymphoma, cystic fibrosis and atypical mycobacterial infections.