Encysive Pharmaceuticals today announced the presentation of data from a clinical study of Thelin(TM) (sitaxsentan) in pulmonary arterial hypertension (PAH), at the European Society of Cardiology Annual Congress in Munich.
Data from the extension of Encysive's multi-center, pivotal Phase IIb/III STRIDE-1 (Sitaxsentan To Relieve ImpaireD Exercise) clinical trial was presented by clinical investigator Adaani Frost, M.D., Baylor College of Medicine, Houston, on Tuesday, August 31.
"The long-term evaluation results presented by Dr. Frost suggest that patients may continue to benefit from Thelin with chronic therapy, which we believe provides valuable information to the physician and patient communities in PAH," said Bruce D. Given, M.D., President and Chief Executive Officer of Encysive Pharmaceuticals. "In order to explore the full therapeutic potential of Thelin, our strategy has been to evaluate Thelin in the broadest population ever for this drug class, and to follow its long-term impact closely."
In the abstract entitled, "Long-term Sitaxsentan Therapy in Pulmonary Arterial Hypertension (PAH)" (E. Horn, et al.), data from the STRIDE-1 trial extension was analyzed to assess the time course to clinical improvement or deterioration with Thelin at doses of 100 mg and 300 mg.
Following treatment with a mean duration of 26 weeks and a maximum of 58 weeks, 53% of the 79 patients on 100 mg and 44% of the 91 patients on 300 mg improved at least one New York Heart Association (NYHA) functional class. A substantial portion of those individuals that improved did so within the initial 12 weeks of therapy -- 64% for 100 mg and 70% for 300 mg. During the first 12 weeks, liver-function abnormalities greater than three times the upper limit of normal occurred in 0% for 100 mg and 10% for 300 mg. Overall rates of 5% for 100 mg and 21% for 300 mg were reported for the entire treatment course. During treatment, only 5% of patients on 100 mg and 8% on 300 mg experienced NYHA functional class deterioration. While both doses of Thelin(TM) are similarly effective in improving functional class, both short- and long-term, the more favorable safety/efficacy profile of 100 mg lends further support to its selection as the maximum clinical dose in ongoing trials of Thelin.
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 targeting the endothelin A receptor.
Pulmonary arterial hypertension (PAH) is a condition involving high blood pressure and structural changes in the walls of the pulmonary arteries, the blood vessels that connect the right side of the heart to the lungs. PAH causes shortness of breath, limits activity, and is eventually fatal unless treated successfully with heart and lung transplants. Primary and secondary PAH are estimated to afflict approximately 80,000 to 100,000 people worldwide, many of whom are children and young women.
Side effects of Thelin seen in the program to date, and which occurred more frequently than in placebo, include liver dysfunction (increased ALT and AST), headache, edema, constipation, nasal congestion and flushing. Because Thelin inhibits the metabolism of warfarin, the dose of warfarin should be adjusted downward when co-administered with Thelin.