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DURHAM, N.C. -- A treatment that had shown early promise in
alleviating symptoms and preventing the advance of the fatal
lung disease pulmonary fibrosis failed to stall the disorder's
progression in 162 patients, according to the results of an
international clinical trial reported in the Jan. 8, 2004,
issue of The New England
Journal of Medicine.

Despite the treatment's failure to prevent scarring of the
lungs -- a defining characteristic of the disease -- results of
the trial did suggest that the drug, known as interferon
gamma-1b, might extend the lives of select patients with mild
to moderate symptoms, said pulmonologist David A. Schwartz,
M.D., who led a portion of the trial at Duke University Medical
Center.

"The bottom-line is that interferon gamma does not appear to
be effective in slowing progression of pulmonary fibrosis (PF),
but could potentially improve survival in patients if caught
early in the disease process," Schwartz said.

The study was funded by InterMune Pharmaceuticals, Inc,
Brisbane, CA, which manufactures interferon gamma-1b. Dr.
Schwartz has been a paid consultant for InterMune since
2000.

PF is an inflammatory disease that results in scarring, or
fibrosis, of the lungs. Over time, the fibrosis can progress
such that the lungs can no longer deliver oxygen to the body's
tissues. Although physicians often treat the disorder with a
combination of anti-inflammatory and immunosuppressive
therapies, the only clearly effective treatment is lung
transplantation, Schwartz said. The median survival time for
patients with the disease is two to three years.

PF has multiple causes including exposure to environmental
contaminants, such as cigarette smoke and asbestos, and genetic
predisposition. The prevalence of the disease is unknown
according the National Institutes of Health, but estimates
indicate the numbers are rising with as many as 15,000 new
cases of idiopathic PF -- a form of the disease having unknown
causes -- diagnosed yearly in the United States. Idiopathic PF
accounts for approximately 50 percent of all PF cases.

Between September 2000 and October 2001, the researchers
enrolled 330 patients with idiopathic PF at 58 centers in the
United States, Europe, Canada and South Africa. Medical tests
confirmed patients' diagnoses before investigators randomly
assigned each trial participant to a placebo or an interferon
gamma treatment group. Patients received treatment three times
weekly for 60 weeks, during which time their symptoms were
monitored at three-month intervals.

Interferon gamma did not slow the progression of the
disease, the researchers found. The therapy also failed to
improved patients' lung function and quality of life.

However, a subset of patients with milder disease symptoms
did survive longer when receiving the drug treatment than did
those in the placebo group, the team reported, suggesting that
interferon gamma might prove beneficial in a select group of
patients. In a subset of patients with mild PF, 3.5 percent of
those that received the drug treatment died during the period
of study compared to 12.5 percent of those in the placebo
group. Schwartz stressed, however, that further study is
required to confirm this promising finding.

"We had anticipated that the drug would affect disease
progression as had been observed in an earlier, smaller study,"
Schwartz said. "Therefore, we were very surprised to see that
disease progression was unchanged in patients receiving the
drug, while survival was extended in individuals with less
severe impairment of lung function." The previous trial,
reported in the New England
Journal of Medicine in 1999, included just 18 patients from
a single site, Schwartz noted.

The team is planning a follow-up study to further explore
the possibility that the drug might extend the lives of some
patients with PF.

The study's co-authors include Ganesh Raghu, M.D., of the
University of Washington in Seattle; Kevin Brown, M.D., of the
National Jewish Medical and Research Center in Denver;
Williamson Bradford, M.D., and Karen Starko, M.D., both of
InterMune, Inc., Brisbane, CA; Paul Noble, M.D., of Yale
University; and Talmadge King Jr., M.D., of the University of
California, San Francisco.