While there was a consistent trend in favor of Bosentan, the primary endpoint, reduction in morbidity/mortality, was not met (p=0.21). The well characterised safety profile of Bosentan was confirmed.
Bosentan, an orally available dual endothelin receptor antagonist, is already approved worldwide for the treatment of pulmonary arterial hypertension under the brand name Tracleer. In the EU and in other territories, Tracleer is also approved for the reduction of new digital ulcers in patients with systemic scleroderma.
Actelion said that Build-3 (Bosentan Use in Interstitial Lung Disease) is a multicenter, double-blind, randomised, placebo-controlled, parallel group, event-driven morbidity/mortality study evaluating the safety and efficacy of bosentan 125mg bid in IPF patients.
Reportedly, Build-3 enrollment was completed in November 2008 with 616 patients. The study was randomised with 2 Bosentan-treated patients to 1 placebo patient. A total of 252 events were recorded in the study. The primary endpoint was not met (p=0.21), but there were consistent trends in favor of bosentan.
Actelion said that following completion of full data analysis, Build-3 findings is expected to be presented in upcoming scientific congresses and peer-reviewed publications. No further studies with Bosentan in IPF will be undertaken.
Jean-Paul Clozel, MD and CEO of Actelion, said: “We are naturally disappointed with this outcome. While in Build-3 there is a consistent trend in favor of Bosentan, these findings do not support initiating regulatory proceedings.
“We remain convinced that endothelin receptors are important targets for potential future treatments in this poorly understood and rapidly progressing form of pulmonary fibrosis. The results of Build-3 suggest that a more complete blockade of both endothelin receptors – as potentially achieved with macitentan – might be needed.”
The 150 patient exploratory study with Actelion’s tissue-targeting endothelin receptor antagonist, macitentan, is currently enrolling patients with idiopathic pulmonary fibrosis. The study is expected to be fully enrolled later this year and report data in second half of 2011.