CHEST: Idiopathic Pulmonary Fibrosis Responds to Tracleer

SALT LAKE CITY, Oct. 27 -- For selected patients with idiopathic pulmonary fibrosis, drug therapy may offer limited benefit, investigators reported here.

There is no effective therapy for the condition, which is increasing in incidence, according to Kevin Brown, M.D., of National Jewish Medical and Research Center in Denver, Colo., but treatment with Tracleer (bosentan) seems to improve the condition of some.

Specifically, the medication appears to improve oxygenation during exercise for some patients, a finding that was "unexpected," Dr. Brown told a session at CHEST 2006, the meeting of the American College of Chest Physicians.

The finding is based on the BUILD-1 study, a randomized, prospective, placebo-controlled trial that evaluated the safety and efficacy on Tracleer in patients with idiopathic pulmonary fibrosis (IPF). The study showed the drug had safety comparable to that seen in patients with pulmonary hypertension, for which it is approved therapy, Dr. Brown said.

But Tracleer, an orally-available dual endothelin receptor antagonist, failed to meet its primary efficacy objective -a significant improvement in the six-minute walk distance test, he said.

That's not surprising, commented Robert Baughman, M.D., of the University of Cincinnati Medical Center: "There has yet to be a successful trial in idiopathic pulmonary fibrosis that has met its initial target," he said.

But Dr. Baughman, who chaired the session in which Dr. Brown presented his data, said there have been "intriguing" secondary analyses, including the finding of better oxygenation for some patients.

"For that sub-population this is a big plus," he said.

Dr. Brown and colleagues have previously reported that Tracleer resulted in a significant improvement in quality of life after six months of treatment and a trend toward better quality at 12 months.

Also, in a post-hoc analysis of patients with biopsy-confirmed idiopathic pulmonary fibrosis, the researchers found a statistically significant increase on the six-minute walk time test, he said.

For the current analysis, he and colleagues drew on oximeter readings taken during the six-minute walk test at baseline, at six months, and at 12 months. Patients fell into two groups, Dr. Brown said: those who desaturated during exercise and those who did not.

In the latter group, the same proportion "became desaturaters" during the course of the trial, whether or not they were on Tracleer or placebo, Dr. Brown said.

But for some patients in the first group - arguably in worse condition at baseline - treatment with Tracleer had a significant benefit, he said:

• Of the 56 Tracleer patients who desaturated during exercise at baseline, seven (or 12.5%) had better oxygenation (defined as 4% or greater in the SpO₂ reading) at the end of the trial.
• Only one of the 57 placebo patients (or 1.8%) improved.
• The difference was statistically significant at P=0.031, although Dr. Brown cautioned that the numbers are small.
• The seven Tracleer patients with better oxygenation also showed a tendency toward better forced vital capacity.

A new study is under way, Dr. Brown said, in which researchers will examine the effect on Tracleer on subgroups of IPF patients who appeared to show a benefit in the BUILD-1 study.

Dr. Brown and his co-authors have received consulting fees from Actelion Pharmaceuticals Ltd. of Switzerland, the makers of Tracleer.