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Actelion provides update on BUILD-3 study in Idiopathic Pulmonary Fibrosis - Study continues as recommended by the Independent Data and Safety Monitoring Board


ALLSCHWIL/BASEL, SWITZERLAND - Actelion Ltd (SIX: ATLN) today announced that the Independent Data and Safety Monitoring Board (DSMB) has recommended continuation of the pivotal Phase III study BUILD-3, evaluating the efficacy and safety of bosentan (Tracleer®) in patients suffering from idiopathic pulmonary fibrosis.

The DSMB was mandated to perform an efficacy and futility interim analysis of 75% of events in BUILD-3 to assess whether study continuation is warranted based on the primary objective of demonstrating delayed disease worsening or death.

Final study results are expected before the end of 2009.

Notes to the Editor

About Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis is a progressive and usually fatal disease of the lung interstitium. It is estimated that there are around 60,000 patients worldwide with a confirmed diagnosis of idiopathic pulmonary fibrosis (IPF).

In IPF, patients experience progressive dyspnea due to loss of lung function and scarring of the lung. As tissue becomes thicker it causes an irreversible loss of the tissue’s ability to transfer oxygen into the bloodstream. Endothelin-1 besides its potent vasoconstriction properties has direct pro-fibrotic and pro-inflammatory effects. Since endothelin concentrations are elevated in interstitial lung disease, there is also evidence implicating endothelin in this disease.

For patients with IPF outside Japan, there are currently no approved therapies available.

About BUILD-3
BUILD-3 (Bosentan Use in Interstitial Lung Disease) is a multicenter, double-blind, randomized, placebo-controlled, parallel group, event-driven morbidity/mortality study evaluating the safety and efficacy of bosentan 125mg bid in IPF patients. BUILD-3 enrollment was completed in November 2008 with 616 patients.

The study is randomized with two bosentan patients to one placebo patient and is planned to reach 202 events. Following the second interim analysis (75% of events) by an independent Data and Safety Monitoring Board, the study continues as planned. BUILD-3 is conducted under a Standard Protocol Assessment (SPA) with the US FDA.

About BUILD-1
In November of 2005, Actelion reported the results of BUILD-1, a clinical study in idiopathic pulmonary fibrosis. Although not statistically significant for the primary end-point, positive trends for predefined secondary end-points were observed such as the combined incidence of disease progression or death at 12 months (36.1% in the placebo group versus 22.5% in the bosentan group), representing a relative risk reduction of 38% (95% CI, -5 to 63%; p=0,078). [5]

About Tracleer® in Pulmonary Arterial Hypertension (PAH)
Tracleer® (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.

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.

PAH is associated with structural changes in both the pulmonary vasculature and the right ventricle. Recent advances [2] in the understanding of the pathogenic factors leading to the pulmonary vascular disease have led to the development of new therapies targeting specific pathways (the prostacyclin pathway; the endothelin pathway; and the nitric oxide pathway) [3]. The available therapies have positive effects in PAH, but they do not provide a cure, and in many patients the disease will progress. PAH remains a serious life-threatening condition [3,4]. Early recognition and an understanding of the selection and timing of therapeutic options remain critical elements in the optimal management of patients with this disorder.

About Tracleer® in Digital Ulcers (DU)
DUs are a manifestation of the underlying vasculopathy which is central to the pathophysiology of systemic sclerosis (SSc) and pivotal in the development of PAH in SSc, one of the leading causes of death in SSc. Endothelin, a pathogenic mediator, is implicated in the underlying vasculopathy in SSc.

DUs can be a frequent, persistent and debilitating complication of SSc. They are caused by a reduction in the lumen of small bloody vessels that decreases blood flow to the fingers and toes causing open sores. DUs are painful, with a debilitating impact on patients’ daily life, often making it impossible to work and undertake even simple day-to-day activities, particularly those associated with fingertip function. Reducing the occurrence of new DUs is an important and achievable treatment goal in SSc.

In the EU, Tracleer® is indicated to reduce the number of new digital ulcers in patients with systemic sclerosis and ongoing digital ulcer disease. Tracleer® has been shown to improve hand function (i.e. dressing and hygiene) in patients with scleroderma-induced digital ulcers.

Requires attention to two significant safety concerns [1]: 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 controlled distribution.


1. Tracleer® SPC
2. Farber HW; Loscalzo J. Mechanisms of disease: pulmonary arterial hypertension. N. Eng. J. Med. 2004; 351:1655-65.
3. Humbert M; Sitbon O; Simonneau G. Treatment of pulmonary arterial hypertension. N. Eng. J. Med. 2004;351:1425-36.
4. Humbert M; Morrell NW; Archer SL; et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J. Am. Coll. Cardiol. 2004; 43: Suppl. 12: 13S-24S.
5. King T.E. et al. High-resolution computed tomography (HRCT) features correlate with response to bosentan in idiopathic pulmonary fibrosis (IPF): the BUILD 1 study [abstract]. Am J Respir Crit Care Med. 175:A567; 2007.

Actelion Ltd
Actelion Ltd is a biopharmaceutical company with its corporate headquarters in Allschwil/Basel, Switzerland. Actelion’s first drug Tracleer®, an orally available dual endothelin receptor antagonist, has been approved as a therapy for pulmonary arterial hypertension. Actelion markets Tracleer® through its own subsidiaries in key markets worldwide, including the United States (based in South San Francisco), the European Union, Japan, 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’s over 2000 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SIX Swiss Exchange (ticker symbol: ATLN) as part of the Swiss blue-chip index SMI (Swiss Market Index SMI® )


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