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Pirfenidone Phase 3 Results Published Today in The Lancet

Saturday, May 14, 2011 General News J E 4
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- Pirfenidone - represents an appropriate treatment option for patients with idiopathic pulmonary fibrosis -

BRISBANE, Calif., May 13, 2011 /PRNewswire/ -- InterMune, Inc. (Nasdaq: ITMN) today announced the publication of results from two Phase 3 trials demonstrating that treatment with pirfenidone, a novel antifibrotic and anti-inflammatory drug, was associated with favorable effects on lung function, 6-minute walk test distance and progression-free survival (PFS) in patients with mild to moderate idiopathic pulmonary fibrosis (IPF).  IPF is a rare and fatal lung disease affecting more than 200,000 patients in the EU and United States combined, with a survival rate of only 20 percent after five years.  The results were published in the online version of The Lancet on May 13, 2011, and will be published in a later print version.

"These newly-published data document the favorable benefit-risk profile of pirfenidone in patients with IPF, consistent with the recent approval by the European Medicines Agency of pirfenidone for these patients," said Paul W. Noble, Professor of Medicine, Chief, Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University School of Medicine, and lead author of the study.  "Although the results of Study 004 and 006 were not identical and only Study 004 achieved the primary end point, the totality of the data provide compelling evidence of a clinically meaningful treatment effect of pirfenidone, together with a favorable safety profile in patients with IPF."

The CAPACITY Program comprises two multinational, double-blind, placebo-controlled Phase 3 studies (Study 004 and Study 006) that were conducted simultaneously with 779 IPF patients (aged 40-80 years) across 110 centers in Australia, Europe and North America.  Patients were randomly assigned to receive oral pirfenidone (2403 mg/day) or placebo for a minimum of 72 weeks to evaluate the impact of pirfenidone in reducing lung function deterioration in IPF patients.

CAPACITY Study Results

Forced Vital Capacity (FVC) – Primary Study Endpoint

In Study 004 pirfenidone reduced the decline in FVC, an important measure of lung function, in IPF patients (p=0.001).  The mean FVC change at week 72 was -8.0 percent in the pirfenidone group compared to -12.4 percent in the placebo group – a significant difference of 4.4 percent.  In addition, treatment with pirfenidone reduced the proportion of patients with FVC decline of 10 percent or more compared to placebo (35 of 174 patients vs 60 of 174 patients).  Importantly, an FVC decline of 10 percent or more has been reported in multiple studies to be associated with an increased risk of mortality in patients with IPF.  

In Study 006, the difference between groups in FVC change at week 72 was not significant (-9.0 percent in the pirfenidone group compared with -9.6 percent in the placebo group); however, a consistent and statistically significant pirfenidone treatment effect was evident through one year of treatment.  The repeated-measures analysis of percent predicted FVC change over all study timepoints showed a favorable pirfenidone treatment effect in both studies.

The primary endpoint analysis of the pooled population also showed a pirfenidone treatment effect on percent predicted FVC at week 72 (p=0.005).  The mean change was -8.5 percent in the patients in the pirfenidone 2403 mg/day group and -11.0 percent in those in the placebo group, and a smaller proportion of patients had a decline in FVC of 10 percent or more in the pooled pirfenidone group.

Six-Minute Walk Test (6MWT) – Secondary Study Endpoint

Pirfenidone 2403 mg/day significantly reduced decline in 6MWT distance at week 72 in study 006 but not in study 004.  In the pooled population, a 31 percent relative difference was noted between treatment groups at week 72. The minimum clinically important difference in 6MWT distance in patients with idiopathic pulmonary fibrosis has been reported to be 24–45m.  In a post-hoc analysis, 62 (36 percent) of 170 patients in the pirfenidone group and 80 (47 percent) of 170 in the placebo group had a 50m or more decrement in 6MWT distance in study 004 (p=0.049), and 56 (33 percent) of 169 and 79 (47 percent) of 168 patients, respectively in study 006 (p=0.010).  The Mantel-Haenszel relative risk was 0.74 (95 percent CI 0.62–0.89) for overall relative risk in the post-hoc analysis in the pooled population.

Mortality and Progression-Free Survival

Pooled data from the 2 clinical studies showed that numerically fewer overall deaths (6 percent vs. 8 percent) and statistically fewer IPF-related deaths (3 percent vs. 7 percent) occurred in the pirfenidone groups compared to placebo groups on-treatment (p<0.03).

In the pooled analysis, pirfenidone prolonged progression-free survival by 26 percent compared with placebo.

Safety

Study results confirmed pirfenidone as a generally well tolerated, oral treatment with a favorable side effect profile; adverse reactions were generally mild or moderate. The most commonly reported (incidence =10 percent) adverse reactions to pirfenidone compared to placebo were: nausea (32.8 percent vs. 13.3 percent), rash (28.7 percent vs. 8.6 percent), fatigue (22.3 percent vs. 13.3 percent), diarrhoea (21.7 percent vs. 13.5 percent), dyspepsia (16.8 percent vs. 5.5 percent) and photosensitivity reaction (12.2 percent vs. 1.7 percent).

Study treatment was discontinued because of adverse events in 51 (15 percent) of 345 patients in the pooled pirfenidone group and 30 (9 percent) of 347 patients in the pooled placebo group.   Treatment-emergent serious adverse events occurred in 113 (33 percent) of 345 patients in the pooled pirfenidone group and 109 (31 percent) of 347 patients in the pooled placebo group.

About Pirfenidone

Pirfenidone is an orally active, small molecule drug that inhibits the synthesis of TGF-beta, a chemical mediator that controls many cell functions including proliferation and differentiation, and plays a key role in fibrosis.  It also inhibits the synthesis of TNF-alpha, a cytokine that is known to have an active role in inflammation.  

On February 28, 2011, the European Commission (EC) granted marketing authorization for Esbriet® (pirfenidone) for the treatment of adults with mild to moderate IPF.  The approval authorizes marketing of Esbriet in all 27 EU member states.  Esbriet has since been approved for marketing in Norway and Iceland.

Since 2008, pirfenidone has been marketed in Japan as Pirespa® by Shionogi & Co. Ltd.  Pirfenidone is still under investigation for the treatment of IPF in the United States and has not been approved by the U.S. Food and Drug Administration for this use.  InterMune currently plans to conduct ASCEND, a new Phase 3 study, toward the goal of bringing pirfenidone to IPF patients in the United States, and currently expects to enroll the first patient in ASCEND in June 2011.

About IPF

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and ultimately fatal disease that affects approximately 235,000 people in Europe and the United States combined.

IPF is characterized by inflammation and scarring (fibrosis) in the lungs, hindering the ability to process oxygen and is a progressive disease, meaning that over time, lung scarring and symptoms increase in severity.  The median survival time from diagnosis is two to five years, with a five-year survival rate of approximately 20 percent.  Patients diagnosed with IPF are usually between the ages of 40 and 70, with a median age of 63 years and the disease tends to affect slightly more men than women.  

About InterMune

InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology.  InterMune has an R&D portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections.  The pulmonology portfolio includes Esbriet® (pirfenidone), which is now approved in the European Union in adults for the treatment of mild to moderate IPF, a progressive and fatal lung disease.  The hepatology portfolio includes next-generation HCV protease inhibitor and NS5A research programs.  For additional information about InterMune and its R&D pipeline, please visit www.intermune.com.

Forward-Looking Statements

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 commercial launch preparations, anticipated timing of commercial launch and statements regarding the various anticipated durations of patent protection and marketing exclusivity.  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.  

Other 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 Securities and Exchange Commission (SEC) on March 9, 2011 (the "Form 10-K"), and other periodic reports filed with the SEC, including but not limited to the following: (i) risks related to the uncertain, lengthy and expensive clinical development process for the company's product candidates, including having no unexpected safety, toxicology, clinical or other issues and having no unexpected clinical trial results such as unexpected new clinical data and unexpected additional analysis of existing clinical data; (ii) risks related to the regulatory process for the company's product candidates, including the possibility that the results of the proposed new 52-week Phase 3 clinical trial (ASCEND) having an FVC endpoint may not be satisfactory to the FDA for InterMune to receive regulatory approval for pirfenidone in the United States; (iii) risks related to unexpected regulatory actions or delays or government regulation generally; (iv) risks related to the company's manufacturing strategy, which relies on third-party manufacturers and which exposes InterMune to additional risks where it may lose potential revenue; (v) government, industry and general public pricing pressures; and (vi) InterMune's ability to obtain or maintain patent or other proprietary intellectual property protections.  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 www.intermune.com.    

Esbriet® is a registered trademark of InterMune, Inc.

SOURCE InterMune, Inc.

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