Actelion Ltd.'s Macitentan Fails Phase 3 Study

ALLSCHWIL/BASEL, SWITZERLAND - 29 August 2011 - Actelion (SIX: ATLN) announced today that the exploratory Phase II study with macitentan in patients with idiopathic pulmonary fibrosis (IPF) shows a promising safety and tolerability profile of macitentan, no difference being observed between placebo and macitentan with regard to liver enzyme elevations.

The double-blind, randomized, placebo controlled, multicenter study evaluated the efficacy and safety of the 10 milligram (mg) dose of macitentan or placebo in 178 patients with idiopathic pulmonary fibrosis. On average, patients were exposed to study drug for more than 14 months, with a maximum exposure of 24.6 months.

Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: “I am very encouraged to observe that, in this patient population, macitentan displays an excellent safety and tolerability profile, particularly in terms of liver enzyme elevations that are no different from placebo.”

Jean-Paul Clozel concluded: “The 10 mg dose of macitentan is the higher of two doses under evaluation in our ongoing Phase III SERAPHIN study in pulmonary arterial hypertension. I expect this event-driven morbidity / mortality study with over 740 patients to report in the first half of 2012.”

The primary endpoint of the MUSIC study, forced vital capacity, was not met. The company will not initiate a Phase III IPF program. Actelion will analyze the study data in detail to understand certain observations in favor of macitentan such as reduced cough and fewer reported cases of pulmonary hypertension (PH). Following discussions with clinical experts in the field, Actelion will present full study data through scientific publications and decide on potential future exploratory efforts.

About the safety and tolerability profile of macitentan in this exploratory IPF study

The safety set comprised 178 patients (randomized 2:1), who received at least one dose of study treatment. Exposure to study treatment was similar in each group, with an average duration of 14.3 months in the macitentan group (n = 119) and 15.4 months in the placebo group (n = 59).

The dual endothelin receptor antagonist macitentan in this patient population was generally well tolerated. Most notably, there was no difference in liver enzyme elevations between macitentan and placebo. Elevations of liver alanine or aspartate aminotransferases greater than three times the upper limit of normal were observed in 4 macitentan-treated patients (3.4%) and 3 placebo recipients (5.1%).

As in other IPF studies with endothelin receptor antagonists, class-related adverse events more frequent on macitentan than placebo were those related to fluid retention (with only one patient discontinuing study treatment) and decrease in hemoglobin, with these changes judged to be not clinically relevant.

In contrast to the tolerability profile of other endothelin receptor antagonists in previous clinical studies, there were no relevant findings of headache, hypotension, nasopharyngitis, rhinitis and hot flush.

About the exploratory MUSIC study

MUSIC (Macitentan USe in an Idiopathic pulmonary fibrosis Clinical study) a double-blind, randomized, multicenter study evaluated the efficacy and safety of the 10 mg dose of macitentan in patients with idiopathic pulmonary fibrosis. The study enrolled 178 patients, who were exposed to either macitentan or placebo with over 75% of patients exposed for at least 12 months and with a mean exposure of over 14 months.

About macitentan

Macitentan is a highly potent, tissue-targeting endothelin receptor antagonist discovered in an in-house research program. Through complete blockade of tissular endothelin, macitentan is expected to protect tissue from the damaging effect of elevated endothelin, specifically in the cardiovascular system. In preclinical studies, macitentan also exhibited effects suggesting that it maintains the integrity of the vascular wall and improves long-term outcome. Accordingly, macitentan may provide therapeutic benefit in a wide range of cardiovascular indications.

About macitentan in Pulmonary Arterial Hypertension (PAH)

Macitentan is also currently being investigated in SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome), a Phase III study designed to evaluate its safety and efficacy in patients with pulmonary arterial hypertension (PAH) through the primary endpoint of morbidity and all-cause mortality. This is the largest study in PAH patients, with the potential to demonstrate long-term morbidity / mortality outcomes. Global enrollment was completed in December 2009 with a total of 742 patients. The study is event-driven and, based on the progress observed, results should be available in the first half of 2012.

About idiopathic pulmonary fibrosis (IPF)

Pulmonary fibrosis is a progressive and usually fatal disease which may arise idiopathically or in association with underlying diseases like systemic sclerosis. In IPF, fibrosis destroys both the structure and function of the respiratory system. Endothelin has direct pro-fibrotic and pro-inflammatory effects. Since endothelin concentrations are strongly elevated in interstitial lung disease, there is also evidence implicating endothelin in these diseases.

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 [1] 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) [2]. 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 [2, 3]. 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.

References

1. Farber HW; Loscalzo J. Mechanisms of disease: pulmonary arterial hypertension. N. Eng. J. Med. 2004; 351:1655-65.

2. Humbert M; Sitbon O; Simonneau G. Treatment of pulmonary arterial hypertension. N. Eng. J. Med. 2004;351:1425-36.

3. 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.

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 2,500 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®).

For further information please contact:

Roland Haefeli

Senior Vice President, Head of Investor Relations & Public Affairs

Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil

+41 61 565 62 62

+1 650 624 69 36

www.actelion.com

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