First ever placebo-controlled trial

The BREATHE-5 study, evaluating the use of Tracleer (bosentan) in 54 patients with pulmonary arterial hypertension (PAH) related to Eisenmenger’s syndrome, showed that 16 weeks of bosentan treatment significantly increased patients’ exercise capacity and decreased their pulmonary vascular resistance (PVR).

Patients suffering from Eisenmenger’s syndrome develop a severe form of PAH as a complication of their congenital heart defect. This syndrome cannot be treated by any conventional means, including surgery. BREATHE-5 is the first ever multi-centre, randomized, double blind, placebo-controlled study to show benefit in this very sick group of patients.


“Patients with Eisenmenger’s syndrome have a reduced life expectancy and a limited functional capacity. It is extremely encouraging that in this disease finally a drug has shown an improvement in exercise capacity and hemodynamics.” said Professor Nazzareno Galiè, from the Institute of Cardiology, University of Bologna, and one of the BREATHE-5 investigators presenting at CHEST.


The main primary endpoint was to assess the safety of bosentan in these patients, as assessed by mean oxygen saturation. The study results show bosentan did not worsen oxygen saturation with a treatment effect of 1.0% on oxygen saturation (Sp02).


The second primary endpoint, mean change in pulmonary vascular resistance (PVRi), was significantly reduced (treatment effect -472 dyn.sec.cm-5; p=0.04). The secondary endpoint exercise capacity, measured by the six-minute walk test, improved by 34 meters in patients treated with bosentan (p=0.02). The safety profile of bosentan was comparable to that observed in previous clinical trials in PAH.


Dr Michael Landzberg from Brigham and Womens Hospital, Boston and principal investigator for BREATHE-5 commented: “In this area of high unmet medical need, bosentan may be a new treatment option for patients with Eisenmenger’s syndrome.”


About Eisenmenger’s syndrome

Eisenmenger's syndrome is a progressive heart condition and occurs in people who have a congenital heart defect or 'hole in the heart'. Prior to the development of Eisenmenger's syndrome, the heart defect allows blood to flow from the left ventricle to the right (left-to-right shunt), which increases blood flow through the lungs. Over time, damage to the pulmonary vessels causes increased resistance to the blood flow to the lungs (pulmonary hypertension), leading to a reversal of the shunt, with blood flowing from the right to the left side. This phenomenon of pulmonary hypertension and right-to-left shunting is termed 'Eisenmenger's syndrome', or 'Eisenmenger's physiology'.


This flow of blood from the right to the left causes the most recognizable symptom of Eisenmenger’s syndrome, a blue tinge to the skin (cyanosis) resulting from low blood oxygen concentration. The poor oxygenation of their blood severely limits their physical activity. In addition to limiting physical activity, Eisenmenger’s syndrome is associated with organ damage and a higher likelihood of premature death. Currently, no intervention significantly improves the clinical status of these patients.


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Note to the Editor:


About Tracleer in Pulmonary Arterial Hypertension (PAH)

Tracleer, the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) in Who Class III and IV patients to improve exercise capacity and improve time to clinical worsening and made available by Actelion subsidiaries in the United States, the European Union, Japan, Australia, Canada, Switzerland and other markets worldwide.


In clinical trials leading to the marketing approval of the drug, approximately 11% of PAH patients receiving Tracleer experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or of childbearing age who do not use a reliable method of contraception, must not take Tracleer. Monthly pregnancy testing is recommended. Concomitant administration with glyburide is contraindicated.


Actelion Ltd Actelion Ltd is a biopharmaceutical company with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug, Tracleer, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium – the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).

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