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InterMune Discontinues Ovarian Cancer Trial With Actimmune (Interferon Gamma-1b)

BRISBANE, CA -- February 3, 2006 -- InterMune, Inc. announced today the decision to discontinue its GRACES phase 3 clinical trial evaluating the safety and efficacy of Actimmune(R) (interferon gamma-1b) in combination with standard of care chemotherapy in patients with advanced ovarian cancer. This decision was based on the results of an interim analysis conducted by an independent Data Safety Monitoring Board (DSMB).

GRACES was a phase 3 trial comparing carboplatin plus paclitaxel (standard of care chemotherapy) combined with Actimmune to carboplatin plus paclitaxel alone, in the treatment of advanced ovarian cancer, defined as International Federation of Gynecology and Obstetrics (FIGO) stage III or IV. The primary endpoint was overall survival. The last patient completed dosing in mid-2004 and patients are currently in post-treatment follow-up.

After reviewing the results of an analysis of Progression Free Survival (PFS) time and an interim analysis of Overall Survival (OS) time, the DSMB recommended the termination of the ongoing post-treatment follow-up of patients in the study. This recommendation was based on a shorter overall survival time in patients who received Actimmune plus carboplatin and paclitaxel compared to carboplatin and paclitaxel alone (p=0.001). One hundred and sixty-nine out of 426 (39.7%) patients in the Actimmune group died as compared to 128 out of 421 (30.4%) patients who received chemotherapy alone. There was no difference in PFS time between treatment groups (p=0.796).

Less than 2% of patients in each treatment group died during the treatment period. The imbalance in survival time across treatment groups was driven by ovarian cancer-related deaths that occurred during follow-up after completion of the study treatment period.

Based on the data available at the time of the interim analysis, the incidence of deaths unrelated to ovarian cancer was less than 2% overall in the study and was similar between the treatment groups.

Preliminary exploratory analyses suggest that the difference in survival time may be related to dose reductions of carboplatin and paclitaxel. Twenty-four percent of patients in the Actimmune group did not complete all six cycles of carboplatin/paclitaxel compared with 17% of patients in the control group. In addition, more patients treated with Actimmune plus carboplatin/paclitaxel had treatment-limiting adverse events that led to a decrease in dose, interruption, or discontinuation of chemotherapy.

The most commonly occurring treatment-limiting adverse event was neutropenia, which is an expected side effect of Actimmune as well as carboplatin/paclitaxel. The combination of agents with overlapping toxicity profiles may explain this higher rate of dose modifications. Past studies underscore the importance of maintaining the recommended dose of chemotherapy in achieving optimal survival times.

More patients receiving Actimmune plus carboplatin/paclitaxel experienced Grade 3 or Grade 4 adverse events and serious adverse events compared to those patients receiving carboplatin/chemotherapy alone.

"We are disappointed that Actimmune in combination with carboplatin and paclitaxel did not benefit patients with ovarian cancer," said Steven Porter, MD, PhD and Chief Medical Officer of InterMune. "The results from this study suggest that Actimmune, which has generally been well-tolerated in studies across multiple disease states, may exacerbate the dose-limiting toxicities of cytotoxic chemotherapy drugs. Consequently, we have no plans to initiate further studies of Actimmune in oncology or in combination with such chemotherapy regimens."

Dr. Porter continued, "We remain very comfortable with the role of Actimmune monotherapy in our approved indications of chronic granulomatous disease and severe, malignant osteopetrosis, and we continue to be very enthusiastic about our ongoing clinical development program evaluating Actimmune alone for the treatment of idiopathic pulmonary fibrosis (IPF). Our ongoing Phase III INSPIRE trial, which is expected to complete enrollment during the first half of 2006, is designed to test the hypothesis that Actimmune has the potential to improve survival in IPF patients. This hypothesis is based on the results of our completed randomized, placebo- controlled 330-patient Phase III study evaluating Actimmune for the treatment of IPF."

"Since early 2004, we have been focused on bringing innovative medicines to patients suffering from serious pulmonary and hepatic diseases," said Dan Welch, President and CEO of InterMune. "Our business and financial plans included no revenue contribution from Actimmune in oncology, so the decision to terminate our non-core oncology trial has no impact on our plans. We will now continue to focus our resources on our three core programs in pulmonology and hepatology -- our Phase III INSPIRE trial for IPF, our phase 3 pirfenidone program for IPF, and our hepatitis C virus (HCV) protease inhibitor."

About Actimmune
Actimmune is a synthesized version of interferon gamma, a naturally occurring protein believed to stimulate the immune system. InterMune markets Actimmune 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 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, including the product's safety profile, by visiting http://www.actimmune.com


SOURCE: InterMune, Inc.

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