ALLSCHWIL, Switzerland, Dec. 20, 2004 (PRIMEZONE) -- Actelion Ltd (Other OTC:ALIOF) (SWX:ATLN) announced today the publication of the full results of the successful study with Tracleer(r) (bosentan) in scleroderma patients suffering from digital ulcerations in Arthritis and Rheumatism Volume 50, Issue 12, page 3985-3993 by J. H. Korn et al. ("Digital ulcers in systemic sclerosis: Prevention by treatment with bosentan, an oral endothelin receptor antagonist").
In this placebo-controlled multicenter trial, patients receiving Tracleer(r) had a 48 per cent reduction in the number of new digital ulcers during the treatment period (1.4 vs 2.7 new ulcers, p=0.0083). In addition, treatment with Tracleer(r) was associated with significant improvement in hand functionality, such as patients' ability to wash their hands, dress and comb their hair. A further study, RAPIDS-2 is now under way with 190 patients. Unlike RAPIDS-1 this trial will have longer treatment time to assess both prevention and healing. Results are expected in late 2005/early 2006.
Joseph H. Korn, MD, Professor of Medicine and Biochemistry, School of Medicine, Boston University, and lead investigator in the US, said, "The decrease in new digital ulcers with bosentan treatment is a clinically meaningful result. Prevention is likely the best approach to digital ulcers in scleroderma. A decreased ulcer burden means patients will have less pain and improved function of their hands as well as a lower risk of serious finger infection and digital loss. This is potentially an important addition to the therapeutic armamentarium and studies are underway to confirm the results and to examine the effect of bosentan on ulcer healing."
RAPIDS-1 (Randomized Placebo-controlled Investigation of Digital ulcers in Scleroderma) was a placebo-controlled double blind clinical trial evaluating the prevention of ischemic digital ulcers in 122 patients with systemic sclerosis (scleroderma) at 17 centers in Europe and North America. It is also the first specifically designed study to look at prevention of ulcer formation. Furthermore, the study is among a very few to demonstrate clinical efficacy in systemic sclerosis. The proven beneficial effect of bosentan in pulmonary hypertension and the results of RAPIDS-1 that demonstrates the prevention of digital ulcers suggest that the drug may promote vascular function in divergent organ systems.
Tracleer(r), the first orally available dual endothelin receptor antagonist for the treatment of pulmonary arterial hypertension (PAH), a chronic life-threatening condition that severely compromises the function of the lungs and heart is already approved in the US, the European Union, Australia, Canada and Switzerland. Tracleer(r) has also been filed for marketing approval in Japan. Between 15 to 30 per cent of all scleroderma patients develop PAH, the leading cause of mortality in these patients.
Professor Carol Black, CBE, Professor of Rheumatology, Royal Free Hospital London, and lead investigator for the RAPIDS-1 Study Group said, "Bosentan significantly reduces the net ulcer burden and improves the hand functionality of patients with systemic sclerosis and a history of digital ulcers." Prof Black added "that these results suggest that dual endothelin receptor antagonism may be an effective therapeutic strategy for the management of digital ulcers in systemic sclerosis."
Ischemic digital ulcerations are a common complication of scleroderma, which affects about 200,000 patients worldwide. Digital ulceration, a result of blockage of small blood vessels (obliterative vasculopathy) occurs in 25 per cent or more of patients. They are very painful and difficult to heal open sores, occurring on fingers and toes, leaving depressed scars and adversely impacting the ability to perform work and daily activities. In severe cases, where gangrene develops, surgery and amputation may be required.
The safety profile of bosentan in this study was comparable to that observed in previous clinical trials with bosentan.
RAPIDS-2 trial update
In late 2003, Actelion initiated a second pivotal Phase III clinical trial, RAPIDS-2 regarding Tracleer(r) in ischemic digital ulcers secondary to scleroderma. In contrast to the earlier RAPIDS-1 trial, this trial includes an assessment of healing as well as prevention in a population with more severe forms of the disease at the time of enrolment. The treatment time will also be longer in order to assess both prevention and healing. The clinical trial was expected to enroll 180 patients. Enrolment was completed in September 2004 with 190 patients. Results are expected in late 2005 or early 2006.
Note to the Editor:
About Scleroderma
In systemic sclerosis (scleroderma), an autoimmune rheumatic disease, there is increased accumulation of connective tissue in skin and internal organs as well as vascular injury and damage. Complications including pulmonary arterial hypertension (PAH) and digital ulcers are the result of vasculopathy (vascular dysfunction). Endothelin, a pathogenic mediator, is implicated in vascular damage. In addition to causing vasoconstriction, endothelin also has direct deleterious effects, which cause fibrosis, vascular hypertrophy, and inflammation.
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. In Japan, Tracleer(r) has been filed for marketing approval.
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 (SWX:ATLN).
For further information please contact:
Actelion Ltd, Gewerbestrasse 16, CH-4123 Allschwil