As I understand Pirfenidone is not very effective and may not get approval
See the article below.
P.J.LAKHAPATE
plakhapate@gmail.com
American Thoracic Society: Pirfenidone Slows IPF Lung Declines
By Michael Smith, North American Correspondent, MedPage Today
Published: May 20, 2008
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. Earn CME/CE credit
for reading medical news
TORONTO, May 20 -- An investigational anti-fibrotic agent is showing promise in the treatment of idiopathic pulmonary fibrosis (IPF), a researcher said here.
Action Points
* Explain to interested patients that there are no approved treatments for idiopathic pulmonary fibrosis.
* Note that this clinical study suggests a new investigational agent may reduce the rate of decline in lung function in patients with the disease.
* Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
In a randomized, double-blind phase III study, pirfenidone, at either of two doses, significantly reduced (at P<0.05) the loss of lung capacity compared with placebo, according to Takashi Ogura, M.D., of the Kanagawa Cardiovascular and Respiratory Center in Yokohama, Japan.
"I expect our study will guide new therapies for IPF in the future," Dr. Ogura said at a press conference at the American Thoracic Society meeting.
The drug, licensed in the U.S. to InterMune Inc., got fast-track status from the FDA yesterday.
Dr. Ogura said the drug is an anti-inflammatory and an anti-oxidant, but that its key mechanism of action in IPF is anti-fibrotic.
After promising earlier studies, he and colleagues enrolled 267 patients and randomized them to placebo, or to one of two doses of the drug -- 1,200 and 1,800 milligrams a day.
The primary endpoint of the 52-week study was change from baseline in lung vital capacity, while secondary endpoints included progression-free survival, Dr. Ogura said.
For this study, progression-free survival was defined as a period without either death or a decrease of more than 10% in vital capacity, Dr. Ogura said.
The researchers found that the drug significantly affected vital capacity:
* Patients on placebo lost 70 milliliters more vital capacity on average than did patients getting the higher dose, a difference that was significant at P<0.05.
* Patients on placebo lost 80 milliliters more vital capacity on average than did patients getting the lower dose, also significant at P=0.05.
Also, Dr. Ogura said, progression-free survival was significantly better (at P<0.05) for both treatment groups than for placebo.
There was no significant difference in oxygen saturation at the end of a six-minute walk test nor in the risk of acute exacerbation, he noted.
The most common adverse events were photosensitivity, loss of appetite, dizziness, and elevated gamma-glutamyl transpeptidase, a marker of poor liver function.
While both doses appeared to improve outcomes, it's not clear that the lower dose is as effective as the higher dose, because of the smaller sample size, Dr. Ogura said.
The researchers made the high-dose cohort larger because of a relatively high dropout rate in earlier studies, Dr. Ogura said.
In this study, however, there was a 32% overall dropout rate, broken down into 37% in the high-dose group, 28% in the low-dose group, and 27% in the placebo group.
He said drop-outs in the treatment groups were mainly due to adverse effects, while the patients in the placebo groups tended to stop because of lack of benefit.
The results of the trial, "done in Japanese patients, may represent a sub-population of patients with IPF," said Ganesh Raghu, M.D., of the University of Washington Medical Center in Seattle, who led one of the early studies on the drug.
Among other things, he said, the study allowed patients to use medications such as prednisone as well, rather than "true placebo controls."
He called for further trials "in a well-defined larger patient population with IPF at different clinical stages."
The study was supported by Shionogi & Co. of Osaka, Japan. Dr. Ogura said he had no disclosures.