Actelion, the Swiss pharmaceutical company, is upbeat this week on news that its dual endothelin receptor antagonist Tracleer (bosentan) significantly improves pulmonary vascular resistance in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). To date there has been no medical treatment available for patients with the condition who are considered unsuitable for surgery or whose symptoms persist despite surgery.
New data from the Phase III BENEFiT study presented this week at the American Thoracic Society meeting in San Francisco showed the drug, already approved worldwide for pulmonary hypertension, achieved the primary endpoint of reducing pulmonary vascular resistance in patients with CTEPH (p<0.0001) and also significantly improved cardiac index and other haemodynamic measures. The study included 157 patients from 26 centres in 13 countries who were treated for 16 weeks.
Although, BENEFiT failed to show a significant improvement at 16 weeks in another primary outcome measure – the six-minute walk test – patients did see a reduction in breathing difficulties and a trend to improvement in other markers of disease severity. Commenting on the study, Professor Lewis Rubin of University of California, San Diego, said: “It seems to take longer than 16 weeks for haemodynamic improvements to translate to improvement in functional capacity. These were patients with a lot of comorbid illness. But even though they didn’t walk significantly further than they did before receiving treatment their medical condition improved, they felt better and were less short of breath over the same distance.” At the same ATS meeting, an open-label Italian study of Tracleer in a similar CTEPH patient population found a significant improvement in the six-minute walk test emerged after six months treatment.
Dr Xavier Jais of Antoine Beclere Hospital, Clamart, France who presented the BENEFiT study in San Francisco said the study is continuing as an open-label evaluation and patients continue to be observed for improvement including the 6-minute walk test and effects on mortality.
First medical therapy for orphan disease CTEPH
BENEFiT is the first multicentre double-blind randomised placebo-controlled study to investigate a medical therapy for CTEPH which affects up to 5,000 new cases annually, said Professor Rubin. Although surgery is the best, and a potentially curable, option, up to half of patients referred to some centres are considered unsuitable for surgery, he noted. The condition is widely underdiagnosed and under-referred at an operable stage.
CTEPH results from pulmonary artery obstruction caused by residual thrombotic matter in patients who have experienced a pulmonary embolus. The condition leads to raised pulmonary arterial pressure and ultimately right-sided heart failure. Patients experience severe breathing difficulties and mortality is high with 50% dying within a year of diagnosis.
A spokesman for Actelion said the company will make plans over the next few months for new submissions to the FDA and European regulators to extend licensing for a CETPH indication on the basis of the BENEFiT data.
