InterMune, Inc. (Nasdaq: ITMN) today announced that the results of a comprehensive review of safety data from four clinical studies were presented at the 2009 European Respiratory Society Annual Congress in Vienna, Austria by Dr. Ulrich Costabel of the Ruhrlandklinik, Essen, Germany.
In order to assess the risk-benefit profile of pirfenidone in IPF patients, a comprehensive review of safety was conducted involving two Phase 3 trials (CAPACITY 1 and CAPACITY 2) and two open-label studies (RECAP and PIPF-002). RECAP is an on-going open-label extension study that enrolled 603 patients who completed CAPACITY. PIPF-002 is an on-going long-term, open-label study in 83 IPF patients.
The summary and conclusions from the safety analysis as presented at ERS were:
- A comprehensive review of safety data from four clinical studies showed that treatment with pirfenidone was safe and generally well tolerated
- In the CAPACITY studies:
- The majority of adverse events (AE) were mild to moderate in nature and relatively few patients discontinued treatment due to adverse events.
- A similar incidence of serious adverse events (SAE) was observed in the pirfenidone group relative to the placebo group
- Fewer deaths were observed in the pirfenidone group relative to the placebo group and this difference was driven by a reduction in IPF-related deaths
- GI and skin AE were more common in pirfenidone-treated patients and were generally mild to moderate, transient, and rarely led to treatment discontinuation
- Transaminase (liver enzyme) elevations were slightly more common in the pirfenidone group, generally low-grade and without clinical sequelae (or secondary effect)
- Results from the two open label studies also suggest that long-term pirfenidone therapy is safe and generally well-tolerated
Dr. Costabel commented on the results, "Based on this comprehensive analysis of safety, pirfenidone appears to be safe and generally well tolerated in patients with IPF and for treatment periods longer than 72 weeks. These safety results, coupled with the evidence of a clinically meaningful pirfenidone treatment effect reported in three Phase 3 clinical trials and taken in the context of the urgent unmet medical need for new medicines for IPF patients, suggest that pirfenidone provides a reasonable risk-benefit profile for patients suffering from IPF. The new analysis presented today on the incidence of IPF-related deaths provides further support for the potential role of pirfenidone in the treatment of patients with this devastating disease."
In this analysis of safety, fewer treatment emergent deaths (those occurring after the first dose and within 28 days of the last dose of study treatment) were observed in the pirfenidone group relative to the placebo group, and this difference was driven by a reduction in IPF-related deaths. In this exploratory analysis of pooled results of the two CAPACITY trials, the incidence of IPF-related deaths was 3.5% in the high-dose pirfenidone arm, compared to 7.2% in the placebo arm>
A similar incidence of SAEs was observed in the pirfenidone group relative to the placebo group. In the CAPACITY trials, 32.8% of patients in the 2403 mg/day dose pirfenidone arm experienced a treatment related SAE, compared to 31.4% of patients in the placebo arm.
As observed in previous studies, gastrointestinal and skin adverse events, such as rash and photosensitivity, were more common in pirfenidone-treated patients, were generally mild to moderate in severity, transient, and rarely led to treatment discontinuation.
Liver enzyme (transaminase) elevations were slightly more common in the pirfenidone group than in the placebo group (4.1% and 0.6%, respectively), were generally low grade, rarely led to treatment discontinuation (0.3% of pirfenidone patients discontinued treatment for liver enzyme elevations versus 0.6% of placebo patients) and were without clinical sequelae.
"IPF is a progressive and uniformly fatal lung disease affecting 250,000 Americans and Europeans and for which there is no approved medicine in the United States or Europe," said Dan Welch, Chairman, Chief Executive Officer and President of InterMune. "The comprehensive and generally favorable safety data for pirfenidone presented today, combined with the evidence of a consistent and meaningful treatment effect of pirfenidone observed in three multi-center, randomized, placebo-controlled Phase 3 studies in IPF suggest that if approved for marketing, pirfenidone could play a meaningful role in the treatment of this devastating disease."
Investors and media may access the slides of the ERS presentation via the company website, www.intermune.com, by accessing the Investor Relations section.
Report at ERS of New Data from the Pirfenidone Phase 3 Study in Japan
Poster P666 entitled "Enhanced effects of pirfenidone on the early phase of idiopathic pulmonary fibrosis (IPF)," was presented on Sunday, September 13 by M. Ebina et al. The authors reported that an analysis of the previously reported Phase 3 study sponsored by Shionogi suggested enhanced effects of pirfenidone in the early phase of IPF.
InterMune is preparing a New Drug Application (NDA) for pirfenidone for the treatment of IPF which it expects to submit in the fourth quarter of 2009, to be followed by a Marketing Authorization Application (MAA), which is expected to be submitted to the European Medicines Agency (EMEA) during the first quarter of 2010.