About bosentan
Bosentan (Tracleer®), is an oral dual endothelin receptor antagonist, which is currently approved for the treatment of pulmonary arterial hypertension (PAH), a chronic, life-threatening disorder which severely compromises the function of the lungs and heart. In the United States, Tracleer® is approved for the treatment of PAH Functional Class II-IV to improve exercise capacity and decrease the rate of clinical worsening. Patients with class II symptoms showed reduction in the rate of clinical deterioration and a trend for improvement in walk distance. Physicians should consider whether these benefits are sufficient to offset the risk of liver injury in class II patients, which may preclude future use as their disease progresses. In Europe, Tracleer® is approved for treatment of PAH Functional Class III to improve exercise capacity and symptoms, as well as PAH Functional Class II, where some improvements have also been shown. In the EU, Tracleer® is also indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease.
Bosentan in combination with sildenafil
Current status
The COMPASS program specifically evaluates safety and efficacy of the use of bosentan in combination with sildenafil. Sildenafil is an approved treatment for PAH but one which works by its effect on another pathological pathway of the disease.
Actelion has concluded COMPASS-1, the first clinical trial to provide detailed hemodynamic information on the combination of sildenafil and bosentan.
The COMPASS-2 study is ongoing to investigate the effect on morbidity and mortality of a combination of bosentan with sildenafil compared to sildenafil monotherapy.
Available clinical data
COMPASS-1 demonstrated that adding sildenafil to patients on long-term bosentan therapy produced significant hemodynamic improvements, including a significant reduction in mean pulmonary vascular resistance (PVR) observed 60 minutes after administration of a single dose of sildenafil 25 mg (-15.2% [95% CI: –20.8 to –9.6]; p < 0.0001), and a decrease in the mean total pulmonary resistance (-13.3% [95% CI: –17.0 to –9.6]; p < 0.0001).
Milestones
2007 – COMPASS-1 study results presented at ESC
2006 – COMPASS program initiated
Key scientific literature
Gruenig E. et al. Acute administration of sildenafil in patients with pulmonary arterial hypertension (PAH) treated with bosentan produced a significant hemodynamic response: results of the COMPASS-1 study. European Society of Cardiology (ESC) Congress 2007 Abstract 1012
