Analyses of Pooled Data from Three Phase III Trials of Pirfenidone (Esbriet[®▼]) Show a Favourable and Persistent Treatment Benefit on Disease Progression in Patients with Idiopathic Pulmonary Fibrosis up to 72 weeks

MUNICH, September 9, 2014 /PRNewswire/ --

• Analysis of an open-label extension study reinforces long-term safety & tolerability of pirfenidone 
• Real-world data from ongoing patient registry shows safety to be consistent with clinical trials
   

InterMune^®, Inc. today presented the results of pooled analyses of data from three multinational, randomised phase III trials (ASCEND [Study 016] and CAPACITY [Studies 004 and 006]) that provide evidence of a durable pirfenidone treatment benefit on multiple measures of disease status in patients with idiopathic pulmonary fibrosis (IPF) who continue through up to 72 weeks of treatment. Professor Paul W. Noble, M.D. from the Cedars-Sinai Medical Center, Los Angeles, presented the data at the European Respiratory Society Annual Congress 2014.

Analyses of pooled outcomes at the time of the study primary endpoint, in which patients were treated for 52 weeks in ASCEND and 72 weeks in CAPACITY, show a 52% reduction in the risk of a ≥10% decline in percent predicted forced vital capacity (FVC) or death (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.37-0.63, p<0.001). The analyses also show a 34% reduction in the risk of a ≥50m decline in 6-minute walk distance (6MWD) or death (HR 0.66; 95% CI 0.54-0.82, p<0.001), and the progression-free survival analysis showed the risk of disease progression was reduced by 38% survival (HR 0.62; 95% CI 0.52-0.75, p<0.001) in the pirfenidone group compared with placebo. Additionally, the risk of all-cause mortality was reduced by 37% (HR 0.63; 95% CI 0.41-0.98, p=0.040) and the risk of treatment emergent IPF-related mortality was reduced by 60% (HR 0.40; 95% CI 0.20-0.80, p=0.007) in the pirfenidone group compared with placebo. The risk of a ≥20 point increase in UCSD SOBQ score or death (HR 0.75; 95% CI 0.60-0.93, p=0.007)was decreased by 25% at study endpoint. Safety outcomes were consistent with prior observations.

Paul Noble, Cedars-Sinai Medical Center, Los Angeles, said, "IPF is a chronic, progressive, and irreversible lung disease that requires both urgent and long-term clinical management. This analysis provides compelling evidence to support the long-term efficacy benefits associated with pirfenidone. Coupled with the long-term safety data presented at this meeting, these results will further inform clinical decision making by healthcare practitioners involved in the care of patients with IPF."

Source data for the pooled analyses included all randomised patients receiving 2403 mg/day or placebo (N=1247) and all observations through Week 52 in ASCEND and Week 72 in CAPACITY. To account for differences in trial duration between the ASCEND and CAPACITY studies, a Cox proportional hazards model was used to estimate the magnitude of treatment effect on the following outcomes: time to confirmed ≥10% decline in FVC or death, time to confirmed ≥50 m decline in 6MWD or death, time to ≥20 point increase in the University of California San Diego Shortness of Breath Questionnaire, progression-free survival (time to first occurrence of a confirmed ≥10% decline in FVC, confirmed ≥50 m decline in 6MWD, or death) and four mortality outcomes.

A separate study presented by Professor Ulrich Costabel M.D. from Essen University Hospital in Germany examined the long-term safety of pirfenidone in patients with IPF enrolled in the RECAP study, a long-term, open-label extension study evaluating continued therapy with pirfenidone in patients who completed one of the Phase 3 trials.  Interim analysis of data from this ongoing trial showed that long-term treatment with pirfenidone has a favourable safety profile and is generally well tolerated for up to 4.9 years. The type and frequency of adverse events were consistent with the Phase III trials, as well as the recently presented comprehensive safety analysis in the integrated population from four clinical trials that included patients with up to 8.6 years of exposure to pirfenidone.^[1]

The safety of pirfenidone was also evaluated in an interim analysis of data from 530 patients enrolled in the PASSPORT study, a post-authorisation surveillance study assessing the long-term safety of patients receiving pirfenidone treatment in the clinical setting in Europe. The interim results, presented by Dirk Koschel M.D. of Fachkrankenhaus Coswig in Germany, showed that the safety of pirfenidone in the real-world setting appears to be consistent with that observed in clinical trials.  In this ongoing, observational, prospective, patient registry, pirfenidone was shown to have a favourable safety profile and was generally well tolerated.

About Pirfenidone

Pirfenidone is an orally active, anti-fibrotic agent 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. Pirfenidone also inhibits the synthesis of TNF-alpha, a cytokine that is known to have an active role in inflammation.^[2]

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 authorized marketing in all 28 EU member states. Pirfenidone has since been approved for marketing in Norway and Iceland.  In 2011, InterMune^® launched commercial sales of pirfenidone in Germany under the trade name Esbriet^[®▼], the treatment is now also commercially available in various European countries, including key markets such as France, Italy, Spain and the UK.

Pirfenidone has been marketed as Pirespa^® since 2008 in Japan and since 2012 in South Korea by Shionogi & Co. Ltd.  Under different trade names, pirfenidone is also approved for the treatment of IPF in China, India, Argentina and Mexico.  A full summary of product characteristics can be found on the Electronic Medicines Compendium.^[3]

About Idiopathic Pulmonary Fibrosis 

Idiopathic pulmonary fibrosis (IPF) is an irreversible and ultimately fatal disease characterized by progressive loss of lung function due to fibrosis (scarring) in the lungs, which hinders the ability of lungs to absorb oxygen.^[4],[5],[6]IPF inevitably causes shortness of breath, and a deterioration in lung function and exercise tolerance.^[3],[4],[5] IPF patients follow different and unpredictable clinical courses and it is not possible to predict if a patient will progress slowly or rapidly, or when the rate of decline may change.^[7],[8] Periods of transient clinical stability in IPF, when they occur, inevitably give way to continued disease progression.^[6] The median survival time from diagnosis is 2-5 years,^[4],[6],[7]with a five-year survival rate of approximately 20-40 percent^[6],[9] which makes IPF more rapidly lethal than many malignancies, including breast, ovarian and colorectal cancers.^[8],[10] IPF typically occurs in patients over the age of 45, and tends to affect slightly more men than women.^[11]

About InterMune^®

InterMune^® is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and orphan fibrotic diseases.  In pulmonology, InterMune^® is focused on therapies for the treatment of idiopathic pulmonary fibrosis (IPF), a progressive and fatal lung disease.  Pirfenidone is approved for marketing by InterMune^® in the EU and Canada as Esbriet®^[▼].  Pirfenidone is not approved for marketing in the United States.  InterMune resubmitted the pirfenidone New Drug Application (NDA) to the U.S. FDA on May 23, 2014, to support regulatory registration in the United States.  The resubmission has been accepted by the FDA and assigned a target PDUFA date of November 23, 2014.  The FDA has granted pirfenidone Breakthrough Therapy Designation.  On August 24, 2014, Roche and InterMune^® announced they had entered into a definitive merger agreement for Roche to fully acquire InterMune^® at a price of $74.00 per share in an all-cash transaction. The closing of the transaction is expected to take place in 2014.  InterMune's research programs are focused on the discovery of targeted, small-molecule therapeutics and biomarkers to treat and monitor serious pulmonary and fibrotic diseases.  For additional information about InterMune and its R&D pipeline, please visit http://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, InterMune's expectations regarding the timing for resubmission of its new drug application with the FDA for pirfenidone; the potential to make pirfenidone available as a medicine to IPF patients in the United States and the potential for pirfenidone to play an important role in managing patients with IPF.  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 February 24, 2014 (the "Form 10-K") and other periodic reports filed with the SEC, including but not limited to the following: (i) the 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 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, in particular in connection with our planned resubmission of a Class 2 NDA with the FDA seeking approval of pirfenidone or other government regulation generally; (iv) risks related to our ability to successfully launch and commercialize pirfenidone in the United States, if approved by the FDA and (v) 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 http://www.intermune.com.

References

1. Nathan, S. Long-term Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis (IPF): Integrated Analysis of Data from 4 Clinical Trials. ATS 2014

2. Schafer CJ et al. Eur Respir Review 2011; 97: 20(85 

3. http://www.medicines.org.uk/emc/medicine/26942 

4. American Thoracic Society/European Respiratory Society. Am J Respir Crit Care Med 2002;165:277(304 

5. Raghu G et al. Am J Respir Crit Care Med 2011; 183:788-824 

6. Travis WD et al. Am J Respir Crit Care Med 2013;188:733(748 

7. Kim DS et al. Proc Am Thorac Soc 2006; 3:285(292 

8. Meltzer EB, Noble PW et al.  Orphanet Journal of Rare Diseases, March 2008 Vol. 3. 

9. Bjoraker JA et al. Am J Respir Crit Care Med 1998;157:199(203 

10. American Cancer Society. Cancer Facts and Figures 200911. National Institute of Health & Clinical Excellence. Clinical Guideline 163:Idiopathic Pulmonary Fibrosis. June 2013

11. National Institute of Health & Clinical Excellence. Clinical Guideline 163:Idiopathic Pulmonary Fibrosis. June 2013

MEDIA CONTACTS:

Jim Goff, InterMune, Inc. +1-415-466-2228, jgoff@intermune.com

Sarah Thomas, Weber Shandwick +41-22-879-8500, SThomas@webershandwick.com