ALLSCHWIL, Switzerland, Aug. 9, 2005 (PRIMEZONE) -- Actelion Ltd (Other OTC:ALIOF) (SWX: ATLN) announced today the preliminary result of a double-blind, placebo-controlled, randomized, multi-center, 190-patient Phase III study, RAPIDS-2, with the dual endothelin receptor antagonist bosentan (Tracleer(R)) in systemic sclerosis patients suffering from digital ulceration.
Preliminary analysis indicates that the primary endpoint of reduction in the occurrence of new digital ulcers during the 6-month treatment period was statistically significant. This result confirms the positive findings from an earlier trial, RAPIDS-1.
The study RAPIDS-2 also evaluated the effect on time to healing of existing digital ulceration in this patient population. There was no difference in time to healing between patients receiving placebo and those receiving bosentan. The safety profile of bosentan in this study was comparable to that observed in previous clinical trials and post-marketing experience with Tracleer(R).
Actelion will now fully analyze the data with a view to discussions and filings with regulatory authorities worldwide. Results will also be presented at key international scientific congresses and will be published in peer-reviewed scientific journals.
Fundamental role of dual endothelin receptor antagonism in systemic sclerosis
James R. Seibold, MD, Professor of Internal Medicine and Director of the University of Michigan Scleroderma Program in Ann Arbor, Michigan, the lead investigator for the RAPIDS-2 Study Group, commented: "I am very pleased that the RAPIDS program confirms the role of dual endothelin receptor antagonism with bosentan as a potential therapeutic strategy for the prevention of digital ulcers in systemic sclerosis."
Dr. Seibold added: "This program adds to our understanding of the role of vasculopathy in systemic sclerosis, a disease with multiple devastating manifestations, including pulmonary arterial hypertension PAH, for which bosentan is currently approved."
Isaac Kobrin, MD, Head of Actelion's Clinical Development, commented: "These positive results, combined with previously described benefits of bosentan in patients with PAH due to systemic sclerosis suggest that stimulation of both endothelin receptors may play an important role in the pathogenesis of vascular complications in systemic sclerosis."
Dr. Kobrin added: "With the RAPIDS program, Actelion has once more demonstrated its dedication to advance medical practice in disease areas with high unmet medical need, such as the manifestations of systemic sclerosis. By year end, for example, I expect the results from a double-blind, placebo-controlled, randomized, multi-center study BUILD-2, evaluating the safety and efficacy of bosentan in another major manifestation of systemic sclerosis, pulmonary fibrosis."
About RAPIDS-2
In late 2003, Actelion initiated a second pivotal Phase III clinical trial, RAPIDS-2 (Randomized Placebo-controlled Investigation of Digital ulcers in Scleroderma) regarding Tracleer(R) in ischemic digital ulcers secondary to systemic sclerosis. In contrast to the earlier RAPIDS-1 trial, this trial evaluated prevention and healing in a population with more severe forms of the disease at the time of enrollment. The treatment duration was longer and a withdrawal period was implemented in order to assess the evolution of digital ulcerations after treatment interruption. Enrollment was completed in September 2004 with 190 patients.
About RAPIDS-1
In the fall of 2002, Actelion reported the positive results of the prevention study RAPIDS-1. In this placebo-controlled, double-blind randomized study enrolling 122 patients diagnosed with systemic sclerosis with either a history or active digital ulcerations at the time of enrollment, the use of Tracleer(R) resulted in a significant reduction in the occurrence of new digital ulcers in this patient population. Worldwide, Actelion calculates that there about 5’000 patients whose severity of digital ulcerations require surgery or constant pain medication. The results of RAPIDS-1 were published December 2004 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").
Note to the Editor:
About Digital Ulcerations
Systemic sclerosis is an autoimmune, rheumatic disease causing accumulation of fibrosis in skin and internal organs as well as vascular injury and damage leading to skin thickening and dysfunction of internal organs (200,000 patients worldwide). As a result of the vascular injury, complications like pulmonary arterial hypertension (PAH) and digital ulcers (approx. 5,000 severe cases worldwide every year) can occur. Approx. 25 percent or more of the systemic sclerosis patients suffer at least once in their disease history from digital ulcers. DUs 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 even amputation may be required.
DUs are a result of the reduction of the lumen of small blood vessels (obliterative vasculopathy as observed in the lung) that diminishes the blood flow to the fingers and toes. 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. Tracleer(R), an endothelin receptor antagonist, is effective in treating PAH in scleroderma patients by blocking the detrimental effects of increased endothelin levels.
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, Japan, Australia, Canada, Switzerland and other markets worldwide.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).
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, Japan 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
Investor Contact Roland Haefeli +41 61 565 64 58
+1 650 624 6936
Media Contact Peter Engel +41 61 565 66 28
+1 650 624 6996
http://www.actelion.com
Conference Call
Actelion will host an Investor Conference Call and discussion/Q&A on
Tuesday, 9 August 2005, 15.30 CET / 09.30 a.m. EST / 14.30 BST
Dial: +41 (0)91 610 56 00 (Europe)
+1 (1) 866 291 4166 (U.S.)
+44 207 107 06 11 (U.K.)
Webcast -- Live and replay on demand
Actelion webcasts its Investor Conference Call. On the Web, you may either follow the call live or have the call replayed later on demand. To access the webcast live, simply visit the link on our homepage http://www.actelion.com/ 5-10 minutes before the conference is due to start.
Approximately 60 minutes after the call has ended, the archived investor webcast will be available for replay on the website "Investors/Past Events."