Pirfenidone, an investigational drug (InterMune) that inhibits the synthesis of TGF-beta and TNF-alpha, was associated with positive effects on lung function, 6-minute walk test distance, and progression-free survival in patients with mild-to-moderate idiopathic pulmonary fibrosis, according to a study published in The Lancet.
Pirfenidone, an investigational drug (InterMune) that inhibits the synthesis of TGF-beta and TNF-alpha, was associated with positive effects on lung function, 6-minute walk test distance, and progression-free survival (PFS) in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF), according to the results of 2 phase 3 trials published online in The Lancet, May 13.
Although the results of the 2 studies weren’t identical, the totality of the data provided enough similarity through 1 year that the European Medicines Agency believed there was sufficient evidence to make the drug available to patients in Europe, said 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.
The European Commission (EC) granted marketing authorization for Esbriet (pirfenidone) for the treatment of adults with mild-to-moderate IPF in February. The approval authorizes marketing of Esbriet in all 27 EU member states. Esbriet is the first approved medicine for patients with IPF in Europe. It has since been approved for marketing in Norway and Iceland.
“I think it’s going to be a very good thing for patients in Europe,” Noble said. “I think that the preponderance of the evidence does support that it slows the rate of loss of lung function. The challenge in this process is how does losing less lung function translate to what the patient feels.”
He noted that measuring lung function is just 1 component of quality of life. “One of the aspects of the trial was that even though we did see a slower rate of decline in lung function, there really was no impact on our measures of quality of life. It’s still an area we’re working through,” he said.
As there is currently no drug in the United States that physicians can prescribe to patients with IPF, Noble believes it will be interesting to see what happens in Europe as the drug becomes available. “I think everybody would agree that if you have this disease and your lung function declines at a slower rate then that’s a good thing,” he said.
The phase 3 study, called the CAPACITY Program, comprised 2 multinational, double-blind, placebo-controlled studies (Study 004 and 006), which were conducted simultaneously for 72 weeks. The studies enrolled a total of 779 patients, aged 40 to 80 years old, with IPF. Patients were randomly assigned to receive oral pirfenidone (2,403 mg/day) or placebo to evaluate the impact of the drug in reducing lung function deterioration.
In Study 004 pirfenidone significantly reduced the decline in forced vital capacity (FVC), an important measure of lung function, in IPF patients. The mean FVC change at week 72 was -8.0% in the pirfenidone group compared with -12.4% in the placebo group. In Study 006, at 72 weeks the difference between groups in FVC change was not significant (-9.0% in the pirfenidone group compared with -9.6% in the placebo group); however, a consistent and statistically significant pirfenidone treatment was evident through 1 year of treatment.
Additional results indicated that pirfenidone 2,403 mg/day significantly reduced decline in 6MWT distance at week 72 in Study 006 but not in Study 004. Also, pooled data showed that statistically fewer IPF-related deaths (3% vs 7%) occurred in the pirfenidone groups compared with placebo groups.
Pirfenidone is still under investigation for the treatment of IPF in the United States and has not been approved by FDA for this use. InterMune currently plans to conduct a new phase 3 study, called ASCEND, aimed at bringing pirfenidone to IPF patients in the United States. The company expects to enroll the first patient in ASCEND in June 2011.
Noble is a consultant for InterMune, as well as for other companies that are involved in developing treatments for IPF.