InterMune, Inc. announced results from two Phase 3 trials demonstrating treatment with pirfenidone was associated with favorable effects on lung function and progression-free survival (PFS) after a six-minute walking test in patients with mild to moderate idiopathic pulmonary fibrosis (IPF).
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 said, “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 provides compelling evidence of a clinically meaningful treatment effect of pirfenidone, together with a favorable safety profile in patients with IPF.”
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.
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 to 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.
In Study 004 pirfenidone reduced the decline in Forced Vital Capacity (FVC), an important measure of lung function, in IPF patients (p=0.001). 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 was evident through one year of treatment.
Pirfenidone 2403 mg/day significantly reduced decline in Six-Minute Walk Test distance at week 72 in study 006 but not in study 004. Study results confirmed pirfenidone as a generally well tolerated, oral treatment with a favorable side effect profile; adverse reactions were generally mild or moderate. 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.
The results were published in the online version of The Lancet on May 13, 2011, and will be published in a later print version.
Release Date: May 13, 2011
Source: InterMune, Inc.
Filed Under: Drug Discovery