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.
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.
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.
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.
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