Actelion's PGI2 receptor agonist demonstrates efficacy in pulmonary arterial hypertension patients - Morbidity-Mortality Phase III study to be initiated before year-end

Corporate news announcement processed and transmitted by Hugin AS. The issuer is solely responsible for the content of this announcement. ---------------------------------------------------------------------- -------------- ALLSCHWIL, SWITZERLAND - 17 July 2009 - Actelion Ltd (SIX: ATLN) announced today that positive data have been obtained in a Phase IIa study with its first-in-class orally active non-prostanoid PGI2 receptor agonist in pulmonary arterial hypertension (PAH) patients. In the 43 patient placebo-controlled double-blind study to assess efficacy, safety and tolerability the primary endpoint of change from baseline in pulmonary vascular resistance (PVR) was met with high statistical significance (P<0.01). The compound was well tolerated in the study. Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "Together with our partner Nippon Shinyaku, we are very excited by the remarkable results we have seen in this study. I am especially pleased as efficacy was achieved on top of background therapy with either an endothelin receptor antagonist and/or a PDE-5 inhibitor. This efficacy with good tolerability makes us determined to accelerate our development program." The positive study results support advancing this first orally active non-prostanoid PGI2 receptor agonist into Phase III. This approach was previously discussed and agreed with the FDA while the study was ongoing. Actelion will now rapidly approach the FDA to finalize the design for a Phase III program with a morbidity/mortality endpoint. Consequently, Actelion expects to initiate this program before year-end. Jean-Paul Clozel concluded: "For the last 30 years, the medical community has been working towards a well-tolerated and effective oral therapy stimulating the prostacyclin pathway. I am very hopeful that in the not so distant future, our PGI2 receptor agonist will make a significant contribution to therapy for this devastating disease." ### Notes to Editor: About the Phase IIa study The study was a multicenter, double-blind, randomized, placebo-controlled study evaluating efficacy and safety of ACT-293987 in PAH patients. The primary endpoint was pulmonary vascular resistance. The study was completed in July 2009 with 43 patients randomized 3:1. 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. Prostacyclin Endothelial cells produce several vasoactive chemical factors, among them prostacyclin (PGI2), which induce vasodilatation of blood vessels and inhibit smooth muscle cell proliferation and platelet aggregation. The peptide endothelin is also produced by the endothelium, and is a potent constrictor of blood vessels and promotes cell proliferation. In a normal healthy state, prostacyclin helps counter-balance the actions of endothelin. In certain disease conditions, however, production of prostacyclin by the endothelium is impaired, allowing the deleterious effects of excessive levels of endothelin to predominate. Prostacyclin receptor Prostacyclin binds the prostacyclin receptor located on the surface of platelets and vascular smooth muscle cells. The receptor is a G-protein coupled receptor that, upon activation by prostacyclin, stimulates the formation of cyclic adenosine monophosphate (cAMP). Dysfunction of the prostacyclin system occurs in several cardiovascular disorders, including thrombosis, myocardial infarction, stroke, myocardial ischemia, atherosclerosis and pulmonary arterial hypertension (PAH). Restoration of prostacyclin function using prostacyclin analogues that activate IP receptors improves prognosis for patients with PAH. Prostacyclin counteracts the vasoconstrictor and pro-thrombotic activity of endothelin. Actelion is developing an orally available and long-acting non-prostanoid PGI2 receptor agonist that mimics the actions of endogenous prostacyclin for the treatment of PAH. 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. About the Actelion / Nippon Shinyaku alliance Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in April 2008 to collaborate on an orally-available long-acting prostaglandin I2 (PGI2) receptor agonist for patients suffering from pulmonary arterial hypertension (PAH). This compound was originally discovered and synthesized by Nippon Shinyaku. Phase I evaluation has been completed, and a Phase II program in PAH patients was initiated by Nippon Shinyaku in Europe at the end of 2007. Actelion will be responsible for global development and commercialization of the PGI2 receptor agonist outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku For further information on Nippon Shinyaku please visit: 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®). For further information please contact: Roland Haefeli Vice President, Head of Investor Relations & Corporate Communications Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil +41 61 565 62 62 +1 650 624 69 36 --- End of Message --- Actelion Pharmaceuticals Ltd Gewerbestrasse 16 Allschwil Switzerland WKN: 936767; ISIN: CH0010532478; Index: SBIOM, SLIFE, SMCI, SMIEXP, SMIM, SPI, SPIEX; Listed: Main Market in SIX Swiss Exchange;