Promising drug fails to thwart fatal lung disease in large trial

January 07, 2004

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.

Duke University Medical Center

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