BRISBANE, Calif., July 7, 2011 /PRNewswire/ -- InterMune (NASDAQ: ITMN) today announced that patient enrollment has begun in ASCEND, a new Phase 3 study of pirfenidone for patients who suffer from idiopathic pulmonary fibrosis (IPF). ASCEND is a multinational, randomized, double-blind, placebo controlled Phase 3 trial designed to evaluate the safety and efficacy of Esbriet® (pirfenidone) in IPF patients with mild to moderate impairment in lung function. The primary endpoint is lung function, as measured by change in forced vital capacity (FVC) from baseline to Week 52. The trial will enroll a total of approximately 500 patientswho will be randomly assigned 1 to 1 to receive oral pirfenidone (2403 mg/day) or placebo. Patients will be enrolled at centers in the United States, Mexico, South America, Australia and New Zealand.
Steve Porter, M.D., Ph.D., Chief Medical Officer of InterMune, said, "We are very pleased to report enrollment of the first patient in ASCEND. This study represents our continued commitment to making Esbriet available for the more than 100,000 IPF patients in the United States who are afflicted with IPF but currently have no FDA-approved therapies available to them."
ASCEND Phase 3 Trial
InterMune's new Phase 3 study of pirfenidone is named ASCEND (Assessment of Pirfenidone to Confirm Efficacy and Safety in IPF). ASCEND will add to pirfenidone's body of clinical evidence and support a future submission for FDA approval.
InterMune expects the trial to be fully enrolled by the first half of 2012, and that results from the study will be available in mid-2013. InterMune anticipates a New Drug Application (NDA) resubmission for pirfenidone in the second half of 2013 and an FDA action in the first half of 2014.
Relative to InterMune's previous studies of pirfenidone in IPF, the entry criteria for ASCEND have been refined to enrich the study population for patients who are more likely to experience decline in lung function and disease progression during the study. InterMune believes that enrolling patients whose disease is more likely to progress will provide greater opportunity to demonstrate a treatment effect in a one-year study.While the entry criteria have been refined, the study is conservatively powered based on the intent-to-treat analyses from the previous CAPACITY Phase 3 program.
Patient eligibility criteria for ASCEND include the following:
- Centrally confirmed diagnosis by High Resolution Computed Tomography (HRCT) (+/- surgical lung biopsy)
- HRCT extent of fibrosis greater than emphysema
- %FVC 50% - 90%
- %DLco 30% - 90%
- FEV1/FVC ratio greater than 0.80
•Time since IPF diagnosis greater than six months and less than four years
The primary endpoint in the ASCEND study is change in percent predicted FVC, with the primary outcome analysis a Rank ANCOVA at Week 52. The magnitude of effect will be presented on a categorical basis as the proportion of patients with decrements of less than 0% or greater than 10% at pre-specified study time points.
Key secondary endpoints include change in six-minute walk test (6MWT) distance and progression-free survival, which will be based on the earliest of time to death, FVC decrement of 10% or greater, or decrement in 6MWT distance of 50 meters or more.
Other secondary endpoints include all-cause mortality, evaluated both independently as well as pooled with the previous CAPACITY data, and on-treatment IPF-related deaths, which also will be evaluated independently and pooled with the CAPACITY data, and dyspnea.
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.
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 of Esbriet in all 27 EU member states. Esbriet has since been approved for marketing in Norway and Iceland.
Since 2008, pirfenidone has been marketed in Japan as Pirespa® by Shionogi & Co. Ltd. Pirfenidone is still under investigation for the treatment of IPF in the United States and has not been approved by the U.S. Food and Drug Administration for this use.
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating and ultimately fatal disease that affects approximately 235,000 people in Europe and the United States combined. IPF is characterized by inflammation and scarring (fibrosis) in the lungs, hindering the ability to process oxygen 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 percent. 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.
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and fibrotic diseases. In pulmonology, we are focused on therapies for the treatment of idiopathic pulmonary fibrosis (IPF), a progressive and fatal lung disease. Pirfenidone, the only medicine approved worldwide for IPF, is approved for marketing by InterMune in the EU as Esbriet® and is currently in a Phase 3 clinical trial in the United States. Pirfenidone is also approved for the treatment of IPF in Japan, where it is marketed by Shionogi & Co. Ltd. under the trade name Pirespa®. 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 www.intermune.com.