Encysive Pharmaceuticals announced top-line results from Stride-6, a clinical study of Thelin (sitaxsentan) in patients with pulmonary arterial hypertension (PAH) who discontinued treatment with bosentan due to lack of efficacy or for safety reasons. The data suggests Thelin may provide important benefits to this patient group.
Stride-6 enrolled 48 patients, 35 of which had discontinued bosentan therapy for lack of efficacy and 13 for reasons related to safety. The mean duration of prior bosentan treatment was 13.4 months (0.1 months - 39 months). Of the 48 patients, 24 were randomized to blinded treatment with 50 mg Thelin once daily and 24 to 100 mg Thelin once a day. Five subjects discontinued the trial early due to disease progression. Of the 48 patients, 45 continued Thelin therapy in a long-term extension trial (Stride-3).
Patients were categorized as improved if their distance walked in six minutes increased by 15 per cent or more after 12 weeks of therapy and as deteriorated if their distance walked declined by 15 per cent or more. Patients with lesser increases or declines were considered unchanged.
Of the 35 patients discontinuing bosentan therapy for lack of efficacy, 33 per cent in the Thelin 100 mg group and 10 per cent in the Thelin 50 mg group improved. Continued deterioration was noted in 20 per cent of the 100 mg group and 15 per cent of the 50 mg group. The remaining patients were considered unchanged, according to a company release.
"Patients failing bosentan, either for efficacy or safety, represent a common and important challenge for treating physicians," reported Dr. Robyn Barst, professor of Paediatrics at Columbia University College of Physicians and Surgeons, and director, New York Presbyterian Hospital Pulmonary Hypertension Centre. He added, "It appears that the 100 mg dose of sitaxsentan may be able to improve up to 1/3 of efficacy failures with bosentan. It further appears that patients developing liver function abnormalities on bosentan may be treatable with sitaxsentan without significantly increased risk of having these abnormalities recur. If substantiated in broader clinical practice, this would be an important finding."
"Stride-6 was designed to give clinicians important information about potential alternatives for those patients who fail on bosentan," Bruce D Given, president and CEO of Encysive Pharmaceuticals commented adding, "This information, when added to the forthcoming results of our phase III pivotal trial and other ongoing trials, should provide for a comprehensive review of the utility of Thelin in the broadest patient population studied to date in a pre-approval setting."
Thelin is a small molecule that blocks the action of endothelin, a potent mediator of blood vessel constriction and growth of smooth muscle in vascular walls. Endothelin receptor antagonists may prove to be effective in the treatment of a variety of diseases where the regulation of vascular constriction is important. Thelin is 6,500 fold selective in the targeting of the endothelin A receptor.
Pulmonary arterial hypertension (PAH) is a condition that involves high blood pressure and structural changes in the walls of the pulmonary arteries, which are the blood vessels that connect the right side of the heart to the lungs.