VIENNA, Sept. 14 /PRNewswire-FirstCall/ -- InterMune, Inc. 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:
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 (p=0.031; Hazard Ratio = 0.48), indicating that patients treated with pirfenidone had a 52% lower risk of IPF-related death than those treated with placebo. The incidence of treatment emergent death from any cause was 5.5% in the 2403 mg/day pirfenidone arm compared to 8.4% in the placebo arm (p=0.141; Hazard Ratio = 0.65) indicating that patients treated with pirfenidone had a 35% lower risk of death from any cause than those treated with placebo.
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.
About CAPACITY and RECAP
The CAPACITY program consisted of two multinational, randomized, double-blind, placebo-controlled Phase 3 trials, named CAPACITY 1 and CAPACITY 2, designed to evaluate the safety and efficacy of pirfenidone in IPF patients with mild to moderate impairment in lung function. The primary endpoint of both trials was change in percent predicted Forced Vital Capacity (FVC) after 72 weeks of treatment evaluated with a nonparametric rank ANCOVA analysis. Both trials enrolled patients in North America, Europe and Australia with roughly 75% of the total 779 patients enrolled in North America.
CAPACITY 1 enrolled a total of 344 patients. Patients were randomized 1:1 to receive a total daily dose of 2403 mg pirfenidone, or placebo. CAPACITY 2 enrolled a total of 435 patients, and patients were randomized 2:2:1 to receive a total daily dose of 2403 mg pirfenidone, or placebo, or a total daily dose of 1197 mg pirfenidone, respectively, administered in three divided doses. The lower dose of pirfenidone in CAPACITY 2 provided safety and tolerability data. The pre-specified statistical analysis plan did not call for this low-dose group to be used in comparative analyses of efficacy. The pooled analyses of the primary and secondary efficacy outcome measures were based on a combined analysis of the 2403 mg group compared with the placebo group across both CAPACITY studies and were considered exploratory.
Enrollment of both trials was completed in less than 13 months following randomization of the first patient into the program in late April 2006. Ninety-seven percent (97%) of all patients in the two CAPACITY studies who were living and had not received a lung transplant, completed their Week 72 study visit.
Regarding RECAP, 603 patients who completed CAPACITY were enrolled in this on-going open-label study. The objective of RECAP is to provide further data on the long-term safety of pirfenidone in patients with IPF.
About Pirfenidone
Preclinical and in-vitro evidence had shown that pirfenidone inhibits collagen synthesis, down-regulates profibrotic cytokines and decreases fibroblast proliferation. Prior to the current results, data were presented from one Phase 3 study and four Phase 2 clinical trials in more than 400 patients which suggested that pirfenidone may positively affect lung function and disease progression in patients with IPF. In those clinical studies, pirfenidone was generally safe and well tolerated with the most frequent side effects reported being photosensitivity rash and gastrointestinal symptoms. In October of 2008, pirfenidone was approved for use in IPF patients in Japan and is marketed as Pirespa(R) by Shionogi in that country.
About IPF
Idiopathic pulmonary fibrosis (IPF) is a disabling and ultimately fatal disease that affects approximately 250,000 patients in the United States and Europe combined, with approximately 30,000 new cases reported per year in each of the United States and Europe.
IPF is characterized by inflammation and scarring (fibrosis) in the lungs, hindering the ability to process oxygen and causing shortness of breath (dyspnea) and cough 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%. 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. There are no medicines approved in the U.S. or Europe for IPF; pirfenidone was approved in Japan in October of 2008.
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 pirfenidone for which a Phase 3 program in patients with IPF (CAPACITY) has been completed and the compound is currently in the pre-registration stage. The company also has a research program focused on a pirfenidone analog named ITMN-520. The hepatology portfolio includes the HCV protease inhibitor compound ITMN-191 (referred to as RG7227 at Roche) that entered Phase 2b in August of 2009 and a second-generation HCV protease inhibitor research program. 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 anticipated product development timelines, the interpretation of the CAPACITY clinical data, including certain exploratory analyses conducted by the Company with respect to such data and the likelihood of regulatory success. 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. Pirfenidone failed to achieve statistical significance on the primary endpoint in one of its two pivotal clinical trials and there can be no assurance that the regulatory authorities in either the United States or Europe will grant regulatory approval based upon these data, in combination with the other efficacy analyses and safety results the company currently intends to submit in support of its NDA and MAA filings. Further analyses of the CAPACITY results will be conducted in the future and additional observations may be made which may lead to material change in the company’s current regulatory strategy for pirfenidone, including a decision by the company not to proceed with either or both of its regulatory submissions in the United States and Europe. These analyses and observations will be included in one or more scientific publications. 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 SEC on March 16, 2009 (the “Form 10-K”) and other periodic reports filed with the SEC, including the following: (i) risks related to the long, expensive and uncertain clinical development and regulatory process, including having no unexpected safety, toxicology, clinical or other issues or delays in anticipated timing of the regulatory approval process; (ii) risks related to failure to achieve the clinical trial results required to commercialize our product candidates; and (iii) risks related to timely patient enrollment and retention in clinical trials. 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.
SOURCE InterMune, Inc.
CONTACT: Jim Goff, InterMune, Inc., +1-415-466-2228, jgoff@intermune.com
Web site: http://www.intermune.com/
