ALLSCHWIL, BASEL, Switzerland, May 19, 2003 (PRIMEZONE) -- Actelion Ltd (Other OTC:ALIOF) (SWX:ATLN) today announced the analysis of long-term follow-up data of primary pulmonary hypertension patients from Tracleer(R) pivotal registration studies. This data suggests that the use of this oral dual endothelin receptor antagonist is associated with improved survival.
Analysis of the data at 36 months found a survival rate of 86 % for patients treated with Tracleer(R) compared to a predicted survival rate of 48 % (1). The difference between observed and predicted values at 6, 12, 24 and 36 months were statistically significant (p less than 0.001) and in favor of treatment with Tracleer(R).
The data presented in the recently published ATS abstract was based upon 26-month data. In a subsequent analysis over a longer time period, additional long-term data of up to 36 months was generated.
These updated results of this first retrospective analysis were presented today at the annual American Thoracic Society meeting in Seattle, Washington, USA by Dr. Vallerie McLaughlin from RUSH-Presbyterian-St. Luke's Medical Center in Chicago.
Dr. McLaughlin presented data collected from the 27 expert sites worldwide that participated in the pivotal studies of Tracleer(R) in PAH. One hundred and sixty nine patients with PPH were followed for a period of up to 39 months, with a median observation time of 25 months.
Commenting on this study, Dr. McLaughlin of RUSH said: "We knew from the pivotal registration studies that treatment with Tracleer(R) provides not only symptomatic benefits, but also decreases the rate of clinical worsening. Now we have new, additional evidence which suggests that the use of Tracleer(R) as a first-line treatment is associated with improved outcome and survival in primary pulmonary hypertension patients."
Professor Gerard Simonneau, of the Hopital Antoine Beclere, Clamart, France, stated: "PAH is a devastating disease with high morbidity and mortality. This data shows that Tracleer(R) not only affects haemodynamics, exercise capacity and symptoms, but also appears to be having a significant impact on the natural history of the disease".
Tracleer(R), the first oral dual endothelin receptor antagonist, is indicated for the treatment of pulmonary arterial hypertension (PAH). PAH patients have high blood pressure in the lungs associated with excessive amounts of endothelin produced in the lungs and blood vessels, causing symptoms that can include breathlessness, chronic fatigue and chest pain.
About the study
In the study, the records of 169 patients with PPH, who were treated with Tracleer(R) and observed for up to 39 months, were collected. The data was taken from a database of two randomized, double blind placebo-controlled studies that led to the approval of Tracleer(R) (2,3) and their open label extensions. The study includes all patients with the primary form of Pulmonary Arterial Hypertension, who continued on Tracleer(R) following the pivotal registration studies.
79 % of the patients were female, and 91 % of the patients were very ill (WHO class III or IV). After data analysis, the observed survival over 36 months was estimated using the Kaplan-Meier statistical method and compared with predicted survival rates by a verified equation based upon the National Institutes of Health (NIH) PPH registry (1). This equation predicts survival based on several measurements, including pulmonary arterial pressure.
Study results
Analysis of the data at 24 months and 36 months found a survival rate of 89 % and 86 %, respectively, for patients treated with Tracleer(R), compared to a predicted survival rate of 56 % and 48 % respectively. The differences between observed and predicted values at 6, 12, 18, 24 and 36 months were statistically significant (p less than 0.001) (4).
113 of the 169 patients were observed for 24 months or more; of these, 90 % were still on Tracleer(R) at the 24-month time-point, either alone or in combination with alternative therapies.
Important safety information In clinical trials, 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 woman of childbearing age, who do not use a reliable method of contraception, must not take Tracleer(R).
About PAH
Around 100,000 people in Europe and the US currently suffer from pulmonary arterial hypertension, which includes PPH or PAH related to other diseases such as scleroderma, a degenerative connective tissue disease (5). Early diagnosis is important for PAH patients. Unfortunately, diagnosis can often be delayed because initial symptoms are unspecific (i.e. breathlessness) and therefore go undetected or are attributed to other diseases.
Tracleer(R)
Tracleer(R), the first oral dual endothelin receptor antagonist, has demonstrated its efficacy in two pivotal, placebo-controlled studies (2,3). Tracleer(R) has shown statistically significant improvements in the primary efficacy endpoint of exercise capacity with patients achieving a significantly greater, and clinically meaningful increase in walking distance compared to placebo.
Clinical trials have also demonstrated Tracleer(R)'s efficacy in significantly decreasing dyspnea (shortness of breath), one of the most debilitating symptoms for people with PAH. Additionally, treatment with Tracleer(R) is also associated with a significant delay in disease progression (the time to clinical worsening) (3). Clinical worsening is defined as combined endpoint of death, hospitalization or discontinuation due to worsening PAH, or initiation of epoprostenol therapy.
Tracleer(R) is currently approved and available in the United States, the European Union, Canada, Australia, Israel and Switzerland for the treatment of Pulmonary Arterial Hypertension (PAH).
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 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
Media Contact Peter Engel +41 61 487 36 28 Investor Contact Roland Haefeli +41 61 487 34 58 +1 650 624-6936 http://www.actelion.com
Conference Call
Dr Vallerie McLaughlin has agreed to present at an Actelion-sponsored conference call and webcast where she will also be available to take questions.
The webcast is taking place on Tuesday, 20 May 2003, 08.00 a.m. (CET) / 02.00 a.m. (EST) / Monday, 19 May 2003, 11.00 p.m. (PST)
Dial: +41 (0) 91 610 56 00 (Europe) +1 412 858-4600 (U.S.) +44 207 107 0611 (U.K.)
Webcast -- Live and replay on demand
To follow Dr McLaughlin's presentation live or to have the call replayed later on demand, simply visit the link on our homepage http://www.actelion.com.
(1) D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115:343-349.
(2) Channick R et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo controlled study. Lancet 2001; 358:1119-23
(3) Rubin LJ, Badesch DB, Barst RJ, Galie N, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002:346:896-903.
(4) McLaughlin V, Sitbon O, Rubin LJ et al. The effect of first-line bosentan on survival of patients with primary pulmonary hypertension. Abstract presented at American Thoracic Society, 2003.
(5) Zaret BL et al. Yale University School of Medicine Heart Book. New York: Hearst Books, 1992. p.178. Koh ET . Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. (1996); Kim N and Rubin L. Endothelin in Health and Diseases: Endothelin Receptor Antagonists in the Management of Pulmonary Arterial Hypertension; J Cardiovasc Pharmacol Therapeut (2002) 7 (I):9-19.