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Improving the quality of life
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Tracleer® – The new cornerstone of PAH treatment
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Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. The function of the heart and lungs is severely compromised, manifested by a limited exercise capacity, and, ultimately, a reduced life expectancy.
Approximately 100,000 people in Europe and the United States are afflicted with either primary PAH or secondary forms of the disease related to conditions or tissue disorders that affect the lungs, such as scleroderma, lupus, HIV/AIDS or congenital heart disease.
The first signs of PAH, such as mild shortness of breath (dyspnea), fatigue and difficulty exercising, are so subtle that the disease is often either misdiagnosed or not diagnosed at all until the patient’s condition is far advanced. Available studies show that, if the disease is left untreated, between 45% and 60% of PAH patients will die within two years of diagnosis.
Tracleer® is the only oral ERA approved for the treatment of PAH. Prior to the availability of Tracleer®, patients who had reached more advanced stages of PAH often had no choice but to go on prostacyclin therapy. This requires a 24-hour infusion pump and an intravenous line implanted through the chest directly into the patient’s pulmonary vein. Ultimately, many patients require lung transplantation.
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Unique competitive situation
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Since endothelin (ET) plays a fundamental role in the development of several diseases, other companies are continuing or starting the development of endothelin receptor antagonists. These are either in the early stages of development or have faced setbacks during the year under review. Actelion’s Tracleer® has been developed as the first oral ERA, specifically targeting ET receptors as pathogenic mediators. As a dual ERA, blocking both ET receptors, ETA and ETB, Tracleer® has a unique potential compared to selective agents currently in development, which only block receptor type ETA.
The use of prostacyclin (epoprostenol), a potent endogenous vasodilator, as a treatment of PAH is supported by a decreased level of prostacyclin in the pulmonary arteries of patients with PAH. Epoprostenol, an agent with a very short half-life, has to be given by continuous intravenous infusion. In the past few years, efforts have been made to simplify the administration of prostacyclins. In 2002, a continuous subcutaneous infusion of Treprostinil (Remodulin®) by mini-pump became available in the United States and Canada. In Europe, efforts have begun to register an inhaled form of prostacyclin (Iloprost). Also in 2002, development in PAH was initiated for the PDE-5 inhibitor sildenafil (Viagra®).
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Raising awareness about the disease
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Since Actelion began preparations for the launch of Tracleer® in 2001, the awareness of PAH has grown enormously among the medical community and media. Our marketing messages have focused on early identification and treatment of PAH. Tracleer® was immediately accepted by experienced PAH physicians as first-line therapy for symptomatic PAH patients. Since then, the referral and prescriber base continues to expand, suggesting long-term growth for Tracleer® in the marketplace in the years to come. In 2002, we successfully increased our educational efforts worldwide, reaching out to the many physicians who are caring for patients at high risk of PAH and emphasizing the need for screening, early diagnosis and effective treatment.
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New hope for patients
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Tracleer® offers PAH patients, for whom even routine breathing is a challenge, an efficacious treatment in a convenient oral form. Tracleer® improves exercise capacity, increasing the ability to perform daily activities without becoming short of breath – which means a dramatic improvement in the patient’s quality of life.
Thirty-nine-year-old Claudia Wochner was a passionate skier until she suddenly recognized that she became short of breath very quickly during her downhill runs. From then on, her physical condition worsened rapidly. “It was frightening to see that I wasn’t able to perform even minor household activities. When my little daughter romped around the house, I couldn’t keep up with her anymore. I was completely out of breath.”
Claudia was lucky that her family doctor was quick to refer her to a lung specialist, who diagnosed PAH and started to treat her with Tracleer®. Since then, her exercise capacity has improved step by step. “Although my doctor tells me that I still have to take it easy because of my health, I already dream about skiing together with my family.”
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Adding valuable clinical data
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The approval of Tracleer® has been supported by two successful clinical studies, both of which were published in The Lancet and The New England Journal of Medicine. Actelion has continued during the year under review to add to this important body of clinical information to support the use of Tracleer® in the marketplace.
In 2002, the results of a preliminary analysis of the clinical trial BREATHE-2 (Bosentan: Randomized Trial of Endothelin Receptor Antagonist THErapy) were disclosed. The study evaluated the safety and efficacy of oral Tracleer® in adult patients suffering from PAH in combination with the initiation of intravenous epoprostenol. The combination of Tracleer® and the initiation of intravenous therapy with epoprostenol was well tolerated and showed a strong trend toward a greater improvement in cardiopulmonary hemodynamic parameters, compared to those receiving epoprostenol alone. These data are important for all patients on intravenous therapy and physicians considering additional therapeutic options.
The BREATHE-3 trial involved children with PAH receiving either Tracleer® alone or in combination with long-term epoprostenol therapy. BREATHE-3 was designed to evaluate the pharmacokinetics, hemodynamics and tolerability of Tracleer® in children under the age of 17 suffering from PAH, either primary pulmonary hypertension or related to congenital heart disease. Results from BREATHE-3, disclosed in 2002, indicated that treatment with Tracleer® alone, and in combination with intravenous epoprostenol, was well tolerated and improved important hemodynamic parameters in children with PAH.
The company has also initiated BREATHE-4, an open-label study to evaluate how Tracleer® can be best used in patients whose PAH is related to their infection with the human immunodeficiency virus (HIV).
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Monitoring for drug safety
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In clinical trials, approximately 11% of PAH patients receiving Tracleer® experienced abnormal but reversible liver enzyme elevations. It is therefore important that patients undergo monthly liver monitoring. Due to the risk of birth defects, women who are pregnant, or who are of childbearing age and do not use a reliable method of contraception, should not take Tracleer®.
In order to ensure adherence to these guidelines, Actelion has developed, together with health authorities, a closed distribution system (US) or a post-marketing surveillance system (EU) to market the drug. Both approaches allow Actelion to continuously remain in contact with treating physicians and their patients to remind them about the importance of adhering to these safety guidelines.
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