SAN DIEGO, May 24, 2005 (PRIMEZONE) -- Actelion Ltd (Other OTC:ALIOF) (SWX:ATLN) announced that data from almost 5,000 Tracleer(R)-treated patients amounting to 3,416 patient-years of treatment were presented on Monday at the American Thoracic Society (ATS) meeting in San Diego. The long-term data collected between May 2002 and November 2004 confirm the safety profile of bosentan as seen in phase III clinical trials and provides information on the combination of treatments such as sildenafil or anticoagulants and bosentan. This data (the TRAcleer(R) eXcellence Post-Marketing Surveillance -- TRAX PMS -- Programme) represents the completion of the largest non-interventional study to date of patients treated with bosentan for PAH in daily medical practice.
Other data presented at ATS show that the addition of sildenafil and atorvastatin to bosentan in PAH patients was well tolerated and showed a trend towards a beneficial effect on exercise tolerance.
PAH is a devastating disease. Untreated, PAH patients die an average of 2.8 years after diagnosis. Tracleer(R) (bosentan) is the first and only approved oral treatment for PAH (Class III and IV) to improve exercise capacity and decrease the time to clinical worsening. Bosentan is a dual endothelin receptor antagonist (ERA). It works by comprehensively blocking the binding of endothelin (ET) to both of its receptors ETA and ETB, thereby preventing the deleterious effects of ET.
Long-Term Safety Profile Consistent with Phase III data
The results from TRAX show that the safety profile of bosentan is consistent with that reported in phase III clinical trials., In particular, liver enzyme measurements showed that elevated ALT and/or AST values were reported in 7.7% of patients compared to 11% as seen in clinical trials and that the likelihood of developing a first aminotransferase elevation decreases over time.(a), Approximately half of those patients with elevated AST and/or ALT values were maintained on bosentan with careful follow-up in line with approved labeling. Of the patients who were rechallenged, the majority were able to continue on bosentan.
Bosentan in Combination with Warfarin is well tolerated
Patients treated for PAH receive various concomitant medications -- disease specific as well as others. Two thirds of bosentan treated patients also received anticoagulants (including coumarin derivatives such as Warfarin). This combination was well tolerated in the long-term experience in daily medical practice.(b)
Adding Sildenafil and Atorvastatin to Bosentan is Well Tolerated
Also presented at ATS, a 12-week double-blind, randomized, placebo-controlled trial of 23 patients already on treatment with bosentan showed that the addition of sildenafil and atorvastatin to bosentan was well tolerated and that the mean treadmill time (459 seconds and 292 seconds, bosentan-combination and placebo, respectively) in patients receiving the active combination improved by 36% (p less than 0.01) compared to an improvement of 27% in the placebo group (p less than 0.05).(c)
The safety profile of patients receiving the combination of bosentan and sildenafil was evaluated by a sub-analysis of the long term TRAX data in 119 patients.(b) Safety findings in this group of patients were comparable to those in patients treated with bosentan. Elevated liver aminotransferase were noted in 7.6% of patients on bosentan plus sildenafil compared with 7.4% in patients receiving bosentan without sildenafil.(b)
Dr Marius Hoeper, University of Hanover Medical School, Germany, commented: "It is important to further confirm if sildenafil can be safely used in patients receiving treatment with bosentan as it would appear to be a useful additional therapy for some patients being treated for PAH."
Regulatory Status for Tracleer(R) in PAH
Tracleer was approved in Europe in May 2002 under exceptional circumstances as a result of positive phase III data. Under these circumstances approval was granted with the provision that ongoing safety was monitored for a period of 3 years. The TRAcleer eXcellence Post-Marketing Surveillance (TRAX PMS) Programme was put in place to record the ongoing safety of bosentan. In the U.S., Tracleer(R) was approved in November 2001 under "sub-part H." Under these circumstances approval was granted with the provision that distribution of Tracleer(R) was restricted. Tracleer(R) has also been approved for the treatment of PAH in Japan, Brazil, Israel and other countries worldwide.
Important information related to prescribing Tracleer(R) in the United States of America:
Indication
Tracleer(R) is indicated for the treatment of pulmonary arterial hypertension in patients with WHO Class III or IV symptoms, to improve exercise ability and decrease the rate of clinical worsening.
Liver and Pregnancy Warnings
Administration of Tracleer(R) requires attention to two significant concerns:
-- Potential for serious liver injury: Liver monitoring of all
patients is essential prior to initiation of treatment and
monthly thereafter; and
-- high potential for major birth defects: Pregnancy must be
excluded and prevented by two forms of birth control; monthly
pregnancy tests should be obtained.
Full prescribing information available at www.tracleer.com or at 1-866-462-2856
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).