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Actelion Pharmaceuticals Ltd (EN) - Investigational dual orexin receptor antagonist almorexant meets primary endpoint in two-week phase III study in patients suffering from primary insomnia

Evidence for differentiation from traditional GABA-agonist zolpidem observed

ALLSCHWIL, SWITZERLAND – 21 December 2009 – Actelion Ltd (SIX: ATLN) announced today that the first phase III study with almorexant (RESTORA 1) has met its primary endpoint, superiority of the dual orexin receptor antagonist almorexant compared to placebo on objective and subjective wake after sleep onset (WASO). The finding was highly significant (p<0.001). In addition, several secondary endpoints of the study were met with statistical significance.

In RESTORA 1, the use of almorexant was well-tolerated. However, in this study as well as in the ongoing non-pivotal program, certain safety observations were made that will require further evaluation and assessment in longer-term Phase III studies. The Phase III studies are currently in preparation - in both adults and elderly patients suffering from primary insomnia - and will evaluate long-term efficacy and safety.

Professor Jed Black, M.D. and VP Sleep Development at Actelion, commented: “In this two-week study, almorexant has demonstrated clinically meaningful effects on both sleep induction and sleep maintenance for patients suffering from primary insomnia. I am especially encouraged that these effects were maintained both throughout the night and throughout the 16-day treatment period.”

Jean-Paul Clozel, M.D and Chief Executive Officer of Actelion, commented: “As a result of the use of an active reference arm of zolpidem 10mg in RESTORA 1, we have now obtained a first promising insight of the impact of our dual orexin receptor antagonist almorexant compared to the impact of a traditional GABA-agonist.”

Jean-Paul Clozel concluded: “Additional studies are being planned to further establish the clinical profile of almorexant. We will explore aspects of sleep quality, absence of addiction and improved next-day performance. Chronic use studies in both adults and elderly will further evaluate the safety profile of this innovative agent.”

About the RESTORA program

Actelion has initiated a comprehensive Phase III program named RESTORA (REstore physiological Sleep with The Orexin Receptor antagonist Almorexant) to evaluate safety and efficacy of 100 and 200 mg doses in adults and elderly patients diagnosed with primary insomnia. The RESTORA program will also include dedicated profiling studies. The non-pivotal program is ongoing. The longer-term Phase III studies are in preparation.


RESTORA 1 was a multi-center, double-blind, randomized, placebo-controlled, active reference (zolpidem), parallel-group polysomnography study to evaluate efficacy and safety of 16-day oral administration of almorexant 200mg and 100mg in adult 709 patients with chronic primary insomnia. Enrolment took place in 90 clinical study centers in Australia, Europe and Israel.

Detailed study results will be made available at upcoming scientific meetings or through publication in peer-reviewed scientific journals.


Notes to the editor

About Orexin Receptor Antagonism

Actelion's research team is targeting the G-Protein coupled receptors (GPCRs) that mediate the actions of orexins. Orexins are neuropeptide modulators produced in the brain to regulate alertness and reward seeking. For example, genetic defects of the orexin peptides, or their receptors, are associated with certain inherited sleep disorders. Orexins have been further associated with food consumption, physical activity, and metabolism in experimental animals. Orexins may also play a role in other conditions.

About Almorexant

Almorexant is a first-in-class dual orexin receptor antagonist which has the potential to shift the paradigm for treating sleep disorders. It is an oral therapy that penetrates the blood-brain barrier and is capable of inducing a transient and reversible blockade of the orexin receptors. Orexins are neuropeptides modulators produced in the brain, or more specifically, by a very small number of specialized neurons located in the hypothalamus. Orexins play an important role in maintaining wakefulness, and therefore regulate the sleep-wake-cycle. Almorexant was discovered by Actelion scientists in an in-house research program.

Actelion and GSK entered into an exclusive worldwide (excluding Japan) collaboration in July 2008 to jointly develop and commercialize Actelion’s first-in-class dual orexin receptor antagonist almorexant.

About the Actelion / GSK alliance

Actelion and GlaxoSmithKline (GSK) entered into an exclusive worldwide (excluding Japan) collaboration in July 2008 to jointly develop and commercialize Actelion’s first-in-class dual orexin receptor antagonist almorexant, a new and targeted treatment approach for insomnia with the potential to restore normal physiological sleep. The compound is currently being developed in the Phase III RESTORA program. The two companies plan to jointly develop and commercialize this novel compound for the treatment of sleep disorders and other orexin-related disorders. Actelion will continue to lead the ongoing Phase III program with almorexant in primary insomnia, with GSK contributing 40 percent of the RESTORA costs. All future costs involving almorexant development and the discovery and development of additional orexin receptor antagonists will be shared equally. In key pharmaceutical markets worldwide, the two companies will both actively promote almorexant, with Actelion booking sales and the two companies sharing profit equally. In emerging markets where Actelion does not plan to build a primary care presence, GSK will promote almorexant on their own, and book sales with Actelion receiving its share of profit.

The two companies will continue their important independent efforts in the field of orexin research and under the agreement can exercise the option to jointly select, develop and promote additional new antagonists targeting the orexin system.

GSK made an upfront payment of CHF 150 million to Actelion in July 2008 and Actelion will be eligible for additional potential milestone payments of up to CHF 415 million contingent on the successful development and approval of almorexant in primary insomnia. In addition, Actelion will be eligible to receive additional milestone payments, pending successful development of two other major indications for almorexant yet to be evaluated through clinical investigation. If all three indications were successfully registered, approved and commercialized, and exceptional sales targets met for all these indications, Actelion would be eligible to receive additional potential milestone payments of up to CHF 2.735 billion.

About sleep disorders

It is widely acknowledged that a lack of sleep can have a significant negative impact on daily functioning, and physical and mental health. There are four main categories of sleep disorder: hypersomnia, circadian rhythm disorders, parasomnias, and insomnia. Insomnia is, worldwide, the most commonly reported sleep disorder, and is estimated to affect up to one third of the adult population.

Most sleep disorder products on the market enhance the effects of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Such medications suffer from a major trade-off: the greater the efficacy, the greater the "hangover" effect the next day in terms of impaired mental and physical performance. Usually, sedatives decrease the length of the REM (rapid eye movement) sleep phase, which – together with non-REM sleep – is hypothesized to be important for memory consolidation.

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? 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).

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

Posted: December 2009