Macitentan (ACT-064992), under development by Actelion Ltd in collaboration with 
Japanese licensee Nippon Shinyaku Co Ltd, is an orally active, non-peptide dual 
endothelin (ET)(A) and ET(B) receptor antagonist for the potential treatment of 
idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). 
Scientific evidence suggests that the ET system may play an important role in 
the pathobiology of several cardiovascular diseases. A major therapeutic advance 
for the treatment of patients with PAH and IPF has been the pharmacological 
control of the activated ET system with ET receptor antagonists. Macitentan, 
because of its ability to target the tissues and to block both ET(A) and ET(B) 
receptors, is emerging as a new agent to treat cardiovascular disorders 
associated with chronic tissue ET system activation. The phase I and II clinical 
trials conducted to date have demonstrated that macitentan increases plasma 
levels of ET-1, displays dose-dependent pharmacokinetics, and was well tolerated 
in healthy volunteers and patients. At the time of publication, a phase II trial 
in patients with IPF and a phase III trial in patients with PAH was ongoing. It 
is expected that the results of these trials will validate the safety and 
efficacy of macitentan.