PIRFENIDONE SLOWS IPF LUNG DELCINES

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ATS: Pirfenidone Slows IPF Lung Declines

By , 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

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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.

Primary source: American Journal of Respiratory and Critical Care

Medicine

Source reference:

Ogura T, et al " Phase III, double-blind, placebo-controlled clinical

trial of pirfenidone in patients with idiopathic pulmonary fibrosis

in Japan " Am J Respir Crit Care Med 2008; 177: A768.

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