Actelion Ltd. discontinued studies of its dual endothelin receptor agonist bosentan in one indication, but intends to move forward with the drug in idiopathic pulmonary fibrosis (IPF) despite missing the primary endpoint in an earlier study.

Bosentan, which is marketed as Tracleer for pulmonary arterial hypertension (PAH), recently completed two trials testing it against IPF and pulmonary fibrosis related to systemic sclerosis. In both trials, the drug failed to show an effect on the primary endpoint of exercise improvement, as measured by the six-minute walk test. But when the secondary endpoints of morbidity and mortality in IPF patients were examined, "we've seen a clear trend in favor of bosentan," Isaac Kobrin, head of development at Actelion, said during a conference call.

In the 158-patient BUILD (Bosentan Use in Interstitial Lung Disease)-1 trial, IPF patients receiving bosentan showed less incidence of death or treatment failure at 12 months (22.5 percent) compared to placebo (36.1 percent) representing a relative risk reduction of 38 percent.

Those results were not statistically significant, but they do provide "a strong rationale" for a morbidity/mortality confirmatory Phase III study in IPF, said Jean-Paul Clozel, CEO of the Allschwil, Switzerland-based company.

"This program is going to become a top priority for the company," he added, "because with these data, we have a light at the end of the tunnel for these patients."

Idiopathic pulmonary fibrosis is a disease that progresses very quickly, and life expectancy following diagnosis is only about three years, Clozel said.

Actelion chose not to start IPF studies focusing on morbidity and mortality because the drug's efficacy in that indication was not known, and those trials typically require large patient populations and extended time periods. The company opted instead to look at exercise improvement.

"But it's clear that the six-minute walk test cannot be used to evaluate the evolution of pulmonary fibrosis," Clozel said.

The company has not yet released details of the upcoming Phase III study, and Clozel said information would be released after details are finalized with the regulatory authorities.

Results from the BUILD-2 study in pulmonary fibrosis related to systemic sclerosis showed no effect on the secondary endpoints. The company attributed this lack of response to the progression of this disease, which is much slower than for IPF, and said it will not pursue the development of bosentan for the systemic sclerosis patient population.

Actelion has several additional development programs for bosentan, investigating the drug in pediatric PAH, PAH in combination with sildenafil, chronic thrombo-embolic pulmonary hypotension, pulmonary hypertension related to sickle-cell disease, digital ulcers related to scleroderma and melanoma.

The company reported a net profit of CHF37.9 million (US$28.9 million), or CHF1.70 per share, for the third quarter of 2005. As of Sept. 30, cash and cash equivalents totaled CHF344 million (US$262 million).

Shares of Actelion on the Swiss Stock Exchange (ATLN) closed at CHF129.20 (US$98.40) Tuesday, up CHF1.80 (US$1.37).