By Elizabeth Mechcatie  |  Wed, 10 Mar 2010 00:37 GMT
Elsevier Global Medical NewsBreaking News SILVER SPRING, Md. (EGMN) – The majority of a Food and Drug Administration advisory panel recommended that pirfenidone be approved as a treatment for patients with idiopathic pulmonary fibrosis. At a March 9 meeting of the FDA’s Pulmonary-Allergy Drugs Advisory Committee, the panel voted 9 to 3 to recommend approval for the proposed indication: reduction in the decline of lung function in idiopathic pulmonary fibrosis (IPF). Those voting in favor of approval agreed that the data on the drug showed treatment was beneficial in slowing the progression of the disease in patients despite conflicting results of two phase III studies. Panelists said, however, that more data are needed to help identify which subsets of patients with IPF may benefit most from treatment and recommended that safety of the drug should be monitored long term, possibly in a patient registry. Pirfenidone, an orally administered drug with an unknown etiology of action, was approved in Japan in 2008 for the treatment of IPF. It has exhibited anti-inflammatory and antifibrotic properties in animal and in vitro studies, according to pirfenidone’s manufacturer, InterMune. The proposed daily dose is 2,403 mg, taken in three divided doses in a capsule formulation. Pirfenidone was compared to placebo in two phase III studies comparing pirfenidone to placebo in almost 800 patients aged 40-80 years (mean age was 67-68 years), with a clinical, radiographic and/or pathologic diagnosis of IPF. The primary end point was the change in the percent predicted forced vital capacity (FVC) from baseline to week 72, which was statistically significant in one of the two studies. In one study, 20% of those treated with 2,403 mg of pirfenidone a day had at least a 10% decline in percent predicted FVC at week 72, compared with 35% of those on placebo, a statistically significant difference. There was no decline in percent predicted FVC at week 72 in 24% of those on the 2,403 mg dosage, compared with 14% of those on placebo, also a statistically significant difference. Progression-free survival, a secondary end point, also favored pirfenidone. But in the other study, there was no significant difference in the percent predicted FVC change among patients treated with 2,403 mg/day of pirfenidone and those on placebo at 72 weeks, although the company pointed out that the differences were significant in favor of pirfenidone at week 48. Nausea and other gastrointestinal side effects and photosensitivity reactions, which were mild to moderate in severity, were more common among those treated with pirfenidone. A total of 14 patients in both studies had liver enzyme elevations, which were reversible and managed by modifying the dose, according to InterMune, which has proposed a risk management plan for prescribing the drug that would minimize the potential risk of hepatotoxicity and photosensitivity reactions. There is no FDA-approved treatment for IPF, a progressive, irreversible diffuse parenchymal lung disease of unknown etiology that is typically diagnosed after age 50. Approximately 100,000 people in the United States have the disease, according to InterMune. The FDA usually follows the recommendations of its advisory panels. Members of FDA advisory panels have been cleared of potential conflicts of interest by the FDA prior to the meeting. Subject Codes: top_stories; pulmonology; gerontology; http://www.imng.com March 09, 2010   07:37 PM EST