Following the European Union marketing approval for Thelin, Encysive Pharmaceuticals Inc has introduced Thelin (sitaxentan sodium) 100 mg tablets in Italy for the treatment of pulmonary arterial hypertension (PAH).
Encysive received European Union (EU) marketing authorization for Thelin from the European Commission in August 2006. Thelin is the first selective endothelin A receptor antagonist, and the first once-daily oral treatment available for patients with PAH.
Thelin is indicated for improving exercise capacity in PAH patients classified as World Health Organization (WHO) functional class III. Efficacy has been shown in primary pulmonary hypertension and pulmonary hypertension associated with connective tissue disease (CTD).
"Italy joins the countries in which two different endothelin receptors antagonists are marketed for the PAH indication," said Nazzareno Galie, M.D., director, Pulmonary Hypertension Centre of the University of Bologna. "The possibility of alternative drugs of the same class can be utilized by clinicians to identify the optimal benefit-to-risk ratio in the individual patient."
The European Commission's centralized licensing procedure permits Encysive to market Thelin in all 27 member states of the EU. Thelin has already been launched in the United Kingdom, Germany, Ireland, Spain, France and the Netherlands and will be launched in additional EU member states as local government approval for reimbursement is obtained.
"The launch of Thelin in Italy marks an important achievement for Encysive Pharmaceuticals," commented George Cole, president and CEO, Encysive. "Thelin is now being commercialised in the five largest markets in the EU, positioning us for substantial sales growth in 2008."
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. Highly selective endothelin A receptor antagonism has been shown to increase blood flow and reverse vasoconstriction in human clinical pharmacology studies.
In placebo-controlled clinical trials, the most frequent adverse events that occurred in patients receiving Thelin, which were considered to possibly be related to Thelin treatment, were headache, peripheral oedema and nasal congestion. Other adverse events that occurred in at least 2 per cent of Thelin patients, at a rate greater than placebo and considered to possibly be related to Thelin treatment, included dizziness, constipation, epistaxis, flushing, international normalized ratio (INR) increase, insomnia, nausea, upper abdominal pain, vomiting, dyspepsia, diarrhoea, fatigue, muscle cramp, and prothrombin time (PT) prolongation. Thelin is also associated with liver function abnormalities. Because Thelin inhibits the metabolism of warfarin and other vitamin K antagonists, a dose adjustment for these drugs is needed when co-administered with Thelin. Thelin and other endothelin receptor antagonists have potential for liver toxicity and are teratogenic. Testing of liver enzymes is required prior to the initiation of Thelin and monthly thereafter. Thelin should not be used during pregnancy unless clearly necessary. 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.
It is estimated that PAH afflicts 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. Since the heart must then pump harder to overcome the resistance, patients are susceptible to heart failure.
Encysive Pharmaceuticals Inc. is a global biopharmaceutical company engaged in the discovery, development and commercialisation of novel, synthetic, small molecule compounds to address unmet medical needs. Our research and development programmes are predominantly focused on the treatment and prevention of interrelated diseases of the vascular endothelium and exploit our expertise in the area of the intravascular inflammatory process, referred to as the inflammatory cascade, and vascular diseases.