Tracleer and PPH News Actelion Provides Update on Bosentan in Japan
Japanese Drug Evaluation Committee Favorably Reviews Tracleer for Pulmonary Arterial Hypertension -- Formal approval expected in early April
-- Market introduction foreseen for spring 2005 ALLSCHWIL, Switzerland, Feb. 28, 2005 (PRIMEZONE) -- Actelion Ltd (SWX:ATLN) today announced that is has received written confirmation that the drug evaluation committee of the Japanese Health Authority (MHLW) issued a favorable review of bosentan (Tracleer(r)) for the indication Pulmonary Arterial Hypertension following their 25 February 2005 meeting. This favorable review is forming the basis on which the Japanese government will issue the formal marketing authorization for Tracleer(r) in the coming weeks. Actelion expects that it could commercially introduce Tracleer(r) in Japan in spring 2005. About Tracleer(r) in Pulmonary Arterial Hypertension (PAH) Tracleer(r), the first oral dual endothelin receptor antagonist, is approved for the treatment of pulmonary arterial hypertension (PAH) and made available by Actelion subsidiaries in the United States, the European Union, Australia, Canada, Switzerland, Israel, Hong Kong, Malaysia, Singapore and Brazil as well as several other smaller territories worldwide. In Japan, Actelion filed for marketing approval of Tracleer(r) in spring 2003. In clinical trials leading to the marketing approval of the drug, approximately 11% of PAH patients receiving Tracleer(r) 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 of childbearing age who do not use a reliable method of contraception, must not take Tracleer(r). About Pulmonary Arterial Hypertension (PAH) 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 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. Actelion Ltd Actelion Ltd is a biopharmaceutical company with its corporate headquarter in Allschwil/Basel, Switzerland. Actelion's first drug Tracleer(r), an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer(r) through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union as well as Canada, Australia and Switzerland. Actelion, founded in late 1997, is a leading player in innovative science related to the endothelium -- the single layer of cells separating every blood vessel from the blood stream. Actelion focuses on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN). For further information please contact: Actelion Ltd, Gewerbestrasse 16, CH-4123 Allschwil CONTACT: Actelion Ltd
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Source: Actelion Ltd
Estrogen-associated COX-2 pathways explain protection from heart disease in female mice
Implications for chronic use of COX-2 Inhibitors in pre-menopausal women - Heart disease is less pronounced in women than in men as humans age, but this difference narrows after menopause. Some studies have shown that estrogen slows heart disease in mouse models, but the mechanism is largely unknown. Now scientists from the University of Pennsylvania School of Medicine show for the first time that in female mice protection from hardening of the arteries purported to come from higher levels of estrogen acts predominately through cyclooxygenase (COX)-2.
Garret FitzGerald, MD, Chairman of the Department of Pharmacology, and colleagues found that estrogen binds to a cell receptor that activates COX-2, which in turn ramps up the production of the prostacyclin PGI2. This biochemical provides protective benefits both by inhibiting platelet activation and by reducing oxidative stress in the circulatory system by increasing expression of an antioxidant enzyme. Earlier experiments in mice by the FitzGerald lab and others have shown that platelet activation and oxidative stress can independently hasten hardening of the arteries. The most recent findings appear in the November 18 issue of Science.
This study shows for the first time that prostacyclin can modulate gender differences in atherosclerosis and that estrogen increases prostacyclin in an animal model. In addition, this research also demonstrates that estrogen upregulates COX-2-dependent prostacyclin and that prostacyclin contributes to the atheroprotective effect of estrogen.
Disabling the prostacyclin receptor in female mice whose ovaries have been removed took away the atheroprotective effect of estrogen. By taking away the ovaries, the investigators can pinpoint the direct effects of estrogen. In mice treated this way, estrogen, as expected, slows hardening of the arteries. Taking away the receptor for PGI2 in those animals largely undermines this protection, which was based on measuring the extent of atherosclerosis. Increased platelet activation was demonstrated by increased levels of the chemical thromboxane, and increased oxidative stress was measured by increases of isoprostanes in the urine.
Because of the direct links among estrogen, COX-2 pathways, and atheroprotection in female mice, this study raises concern about the use of COX-2 inhibitors in premenopausal women. These studies also raise the possibility of an interaction between hormone replacement therapy and drugs which inhibit COX-2, including traditional NSAIDs. Of particular concern for selective inhibitors of COX-2 would be for patients with juvenile arthritis, which involves mostly long-term drug use in young, premenopausal women, says FitzGerald, also Director of the Institute for Translational Medicine and Therapeutics.
Although researchers extrapolate results from mice to humans with extreme caution, recent studies linking COX-2 inhibitors with cardiovascular risk have focused attention on the possibility of slowly evolving cardiovascular risk during chronic treatment with selective COX-2 inhibitors. This study provides insight into how this risk might occur and identifies potential biomarkers of this evolving risk. The work was funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. Other Penn researchers on this paper were Karine M. Egan, John A. Lawson, Susanne Fries, Daniel J. Rader, and Emer M. Smyth, along with Beverley Koller, University of North Carolina.
This release can also be found at: www.uphs.upenn.edu/news.
PENN Medicine is a $2.7 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System (created in 1993 as the nation's first integrated academic health system).
Penn's School of Medicine is ranked #3 in the nation for receipt of NIH research funds; and ranked #4 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three owned hospitals [Hospital of the University of Pennsylvania, which is consistently ranked one of the nation's few "Honor Roll" hospitals by U.S. News & World Report; Pennsylvania Hospital, the nation's first hospital; and Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania Medical Center
http://www.med.upenn.edu
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