Actelion has announced the results of COMPASS-2, a Phase IV, prospective, randomized, double-blind, placebo-controlled, event-driven study evaluating the effect of Bosentan ( Tracleer ) on the time to first morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension ( PAH ) already treated with Sildenafil ( Revatio ).
COMPASS-2 did not meet the primary endpoint of time to first morbidity or mortality event; Bosentan showed a risk reduction of 17% versus placebo ( p=0.25 ).
In an exploratory analysis, bosentan on top of Sildenafil showed an improvement of 21.8 meters in 6MWD at week 16 ( p=0.01 ).
The well characterized safety profile of Bosentan was confirmed and a placebo-corrected incidence of 15.4% in liver enzyme elevations ( aspartate aminotransferase [ AST ] or alanine aminotransferase [ALT ] ) greater than three times the upper limit of normal was observed over a median exposure to double-blind treatment of 23 months.
The primary objective of COMPASS-2 was to demonstrate that Bosentan prolongs the time to first morbidity or mortality event in patients with symptomatic pulmonary arterial hypertension already receiving Sildenafil therapy.
COMPASS-2 was a prospective, double-blind, placebo-controlled, event-driven study evaluating the progression of pulmonary arterial hypertension in two groups of patients already treated with Sildenafil, one group receiving placebo and the second group receiving Bosentan.
Sildenafil and Bosentan are approved treatments for pulmonary arterial hypertension but which exerts their effects through different pathological pathways of the disease.
The study was designed to demonstrate a relative risk reduction of 43% in the primary endpoint.
Pulmonary arterial hypertension is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The symptoms of pulmonary arterial hypertension are non-specific and can range from mild breathlessness and fatigue during normal daily activity to symptoms of right heart failure and severe restrictions on exercise capacity and ultimately reduced life expectancy.
PAH is one group within the classification of pulmonary hypertension ( PH ). This group includes idiopathic PAH, heritable PAH and PAH caused by factors which include connective tissue disease, HIV infection and congenital heart disease.
Three pathways have been established in the pathogenesis of PAH, the endothelin, nitric oxide and the prostacyclin pathways.
PAH treatments targeting these pathways have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance 10 years ago to delayed disease progression today.
Bosentan is the first oral dual endothelin receptor antagonist, approved for the treatment of pulmonary arterial hypertension. ( Xagena )
Source: Actelion, 2014