VIENNA, Austria, Sept. 3, 2007 (PRIME NEWSWIRE) -- At the 2007 European Society of Cardiology (ESC) congress in Vienna, Actelion Ltd (SWX:ATLN) has presented full results from a Phase IIIb trial(1) which demonstrated that six months of treatment with bosentan (Tracleer(r)) in patients with mildly symptomatic WHO functional class II (FCII) Pulmonary Arterial Hypertension (PAH) significantly delayed time to clinical worsening and reduced the number of patients worsening to WHO functional class III/IV.
The 185-patient EARLY (Endothelin Antagonist tRial in miLdlY symptomatic PAH patients) study(1) was a randomized, double blind, placebo-controlled trial and it is the only randomized controlled trial (RCT) to study a dedicated FCII population.
Results from EARLY(1) suggest that PAH is a serious and progressive disease, even in FCII patients who typically present with mild symptoms. The effect of bosentan on time to clinical worsening, an important measure of disease progression, was significant, representing a risk reduction of 77% (p=0.0114). Time to clinical worsening was defined by death; hospitalization for PAH and symptomatic progression of PAH. The relevance of this finding was supported by a significantly lower incidence of worsening of functional class (3.4% vs. 13.2%, P = 0.0285) with bosentan compared to placebo, as well as by improvement in quality-of-life indices.
Furthermore, when compared to placebo, bosentan was shown to significantly reduce pulmonary vascular resistance (PVR), representing a treatment effect of -22.6% (-33.5, -10.0; p less than 0.0001), significantly improve several other important hemodynamic measurements, and showed a strong trend for an effect on exercise capacity (measured by the 6-minute walk distance).
The safety and tolerability profile was consistent with previous placebo-controlled clinical trials in pulmonary arterial hypertension.(2)
Professor Nazzareno Galie from the University of Bologna, Italy, commented: "PAH is a rare but serious disease that progresses rapidly if left untreated. The results of the EARLY study confirm for the first time that early diagnosis and treatment of PAH have an impact on a relevant end-point such as clinical worsening, even for those patients who present with mild symptoms."
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion, added: "The results of the EARLY study reinforce our understanding of PAH as a progressive and serious disease that needs to be diagnosed and treated in the early stages. This is the third successive RCT with Tracleer(r) to provide data that shows a significant effect on delaying time to clinical worsening, a reflection of disease progression. This data is being used as a basis for regulatory submissions worldwide. Actelion will continue its clinical research program to further improve our understanding of PAH disease progression and management."
Findings from other bosentan studies were also presented at the 2007 ESC congress.
COMPASS-1(3) Hemodynamic effects of a single dose of sildenafil in
symptomatic patients on bosentan treatment for PAH
COMPASS-1(3) was the first clinical trial to provide detailed hemodynamic information on the combination of sildenafil and bosentan. Findings showed that the combination of sildenafil together with long-term bosentan therapy produces significant hemodynamic improvements including a highly significant reduction in mean PVR observed 60 minutes after administration of a single dose of sildenafil 25 mg (-15.2% (95% CI: -20.8 to -9.6); p less than 0.0001) and a decrease in the mean total pulmonary resistance (-13.3% (95% CI: -17.0 to -9.6); p less than 0.0001).
FUTURE(4) FormUlation of bosenTan in pUlmonary arterial
hypeRtEnsion
This was a phase III open label, single-arm study(4) of a novel pediatric formulation to characterize the pharmacokinetic profile in children with PAH. The pediatric formulation of bosentan was well tolerated with a safety profile similar to that seen previously in the adult population. The longer-term safety and efficacy continues to be studied in the FUTURE-2 extension study.
BENEFiT Bosentan Effects in iNopErable Forms of chronIc
Thromboembolic pulmonary hypertension (CTEPH)
Results from the BENEFiT trial, a Phase III double blind, randomized, placebo-controlled study in patients with inoperable CTEPH, will be presented on Wednesday, 05 September 2007.
Bosentan is currently licensed for the treatment of pulmonary arterial hypertension (PAH Functional Class III in Europe, Class III and IV in the United States) to improve exercise ability.(5) In the summer of 2007, Actelion has submitted the EARLY data to Health Authorities worldwide for inclusion in the product labeling.
Notes to editors
About Tracleer(r) in Pulmonary Arterial Hypertension (PAH) Tracleer(r) (bosentan), 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(5).
Requires attention to two significant safety concerns: Potential for serious liver injury (including rare cases of liver failure and unexplained hepatic cirrhosis in a setting of close monitoring) - Liver monitoring of all patients is essential prior to initiation of treatment and monthly thereafter. High potential for major birth defects -Pregnancy must be excluded and prevented by two forms of birth control; monthly pregnancy tests should be obtained. Because of these risks, Tracleer is only supplied through a controlled distribution.
Online information on pulmonary arterial hypertension (PAH): www.pah-info.com Online information on pulmonary arterial hypertension (PAH): www.pah-info.com PAH-info.com is part of an international PAH awareness campaign supported by Actelion Pharmaceuticals and has been created to provide healthcare professionals and patients with accurate and continuously updated information on PAH. The website contains information on symptoms, causes, diagnosis and current treatment options in separate sections for healthcare professionals and patients. It also includes a section on Systemic Sclerosis (also known as scleroderma or SSc); a chronic connective tissue disease where PAH is reported in approximately 16% of patients. The website is supported by high-quality resources such as links to an extensive list of worldwide patient associations and professional health organizations and additional sources of information.
Conference Call
Actelion will host an Investor Conference Call and Q&A on Monday, 03 September 2007, 20:00 Cairns (Australian EST) / 12:00 Basel (CEST) / 11:00 U.K. (BST) / 06:00 U.S. (EDT)
Dial: +41 44 580 6403 (Europe)
+1 866 895 8561 (U.S.)
+44 207 153 9962 (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.
Alternatively, copy the following link into your browser: http://gaia.world-television.com/actelion/20070903/trunc
Approximately 60 minutes after the call has ended, the archived investor webcast will be available for replay through our homepage. After 03 September 2007, it will be stored under Investors/Past Events.
References
(1) Galie N, et al. Presented at ESC 2007.
(2) Rubin LJ et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 2002; 346: 896-903.
(3) Gruenig E, et al. Presented at ESC 2007.
(4) Beghetti M, et al. Presented at ESC 2007.
(5) Summary of Product Characteristics available at http://www.emea.europa.eu/humandocs/PDFs/EPAR/tracleer/H-401-PI-en.pdf. Last accessed 15 May 2007.