Canadian Health Authority Approves THELIN (Sitaxsentan Sodium) for Pulmonary Arterial Hypertension
May 30, 2007 17:46:21 (ET)
HOUSTON, May 30, 2007 (PrimeNewswire via COMTEX) -- Encysive Pharmaceuticals (ENCY, Trade ) today announced that Health Canada's Therapeutic Products Directorate has approved THELIN(tm) (sitaxsentan sodium) 100 mg tablets.
THELIN is indicated for the treatment of primary pulmonary arterial hypertension (PAH) and pulmonary hypertension secondary to connective tissue disease, in patients with World Health Organization (WHO) functional class III who have not responded to conventional therapy. THELIN is also indicated in patients with WHO functional class II who did not respond to conventional therapy and for whom no appropriate alternative can be identified.
THELIN is the first selective endothelin A receptor antagonist (ETRA) available, and the only once-daily oral treatment approved for PAH.
PAH is estimated to afflict approximately 100,000 to 200,000 people in North America and Europe. The disease is characterized by 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. As these arteries become increasingly constricted, blood flow and oxygenation may be inadequate to meet the body's demands. The heart must then pump harder to overcome the resistance, and patients become susceptible to heart failure.
"The approval of THELIN represents an advance in the treatment options available for PAH patients in Canada," commented David Langleben, M.D., Professor of Medicine, McGill University and Director of the Center for Pulmonary Vascular Disease, Jewish General Hospital, Montreal. "THELIN's safety and efficacy profile and once-a-day oral formulation make it an attractive therapeutic option, and I look forward to its commercial availability."
"THELIN has demonstrated a unique benefit for individuals who have developed PAH as a result of a connective tissue disease, such as scleroderma," said Janet Pope, M.D., Professor of Rheumatology, University of Western Ontario and Director, Division of Rheumatology, St. Joseph's Health Centre, London, Ontario. "As a clinician, I welcome any new treatment that may help these particular patients, as they are a more difficult group to treat."
THELIN's approval is based on the largest database of patients with PAH ever assembled in an original Canadian New Drug Submission, with more than 1,000 PAH patients receiving THELIN. Encysive received European Union marketing authorization for THELIN in August 2006, marketing approval from the Australian Therapeutic Goods Administration in March 2007 and the drug is currently under evaluation by the Food and Drug Administration (FDA) in the United States.
"This approval is another important step in our effort to commercialize THELIN worldwide," stated Bruce D. Given, M.D., President and Chief Executive Officer of Encysive Pharmaceuticals. "We're extremely proud to have achieved this milestone and look forward to bringing THELIN to PAH patients in Canada."
THELIN(tm) (Sitaxsentan Sodium) Canadian Marketing Authorization Highlights
The Canadian market authorization was based on submitted data from quality (chemistry and manufacturing) studies, as well as data from non-clinical and clinical studies. Two randomized, double-blind, multi-centre, placebo-controlled studies (n=425) were conducted to demonstrate efficacy and safety. Compared to placebo, treatment with THELIN resulted in a significant increase in exercise capacity. The placebo-corrected increases in six-minute walk distance compared to baseline were 35 meters and 31 meters for the two pivotal studies. Compared to placebo-treatment, THELIN demonstrated improvements to the cardiac index, pulmonary vascular resistance, and systemic vascular resistance after 12 weeks of treatment. Compared to placebo-treatment, THELIN improved functional class. A significant reduction in the rate of clinical worsening was also reported in patients treated with THELIN.
In the STRIDE program, THELIN 100 mg was shown to significantly improve exercise capacity, as measured by improvement in six-minute walk distance, including in patients with connective tissue disease. THELIN was also shown to reduce patients' PAH symptoms (improvement in WHO/NYHA functional class) and improve PAH hemodynamic status. Survival of patients was 96% at one year in the overall patient population and 98% in patients with PAH secondary to connective tissue disease.
Important Safety Information
Like other ETRAs, THELIN is teratogenic, and pregnancy must be excluded before the start of treatment and prevented thereafter by the use of a reliable method. Monthly pregnancy tests during treatment with THELIN are recommended. THELIN has a potential for liver toxicity. Testing of liver enzymes is required prior to the initiation of THELIN and monthly thereafter. In placebo-controlled clinical trials, the most commonly reported adverse events with THELIN treatment were headache, peripheral edema, nasal congestion, nausea, constipation, epistaxis, insomnia, prothrombin time prolonged and international normalized ratio (INR) increase. Because THELIN inhibits the metabolism of warfarin, a dose adjustment is needed when co-administered with THELIN. THELIN is contraindicated in patients receiving cyclosporine A, patients with mild to severe hepatic impairment (Child-Pugh Class A-C), patients with elevated liver aminotransferases prior to starting treatment (elevation in liver enzymes to levels greater than 3 times the upper limit of normal), lactating patients, or patients with hypersensitivity to the active substance or any excipients.
THELIN(tm) (Sitaxsentan Sodium) Overview
THELIN is an endothelin A receptor antagonist, 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 versus the endothelin B receptor. Selective endothelin A receptor antagonism has been shown to increase blood flow and reverse vasoconstriction in human clinical pharmacology studies.
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