Actelion and GlaxoSmithKline enter into exclusive collaboration to realise the full potential of almorexant

Actelion and GlaxoSmithKline enter into exclusive collaboration to realise the full potential of almorexant in sleep disorders and beyond

Actelion and GlaxoSmithKline (GSK) to potentially co-develop and co-commercialise other orexin receptor antagonists

ALLSCHWIL, SWITZERLAND and LONDON, UK - 14 July 2008 - Actelion Ltd (SWX: ATLN) and GlaxoSmithKline (LSE and NYSE: GSK) announced today that they have entered into an exclusive worldwide collaboration (excluding Japan) for Actelion's almorexant, an orexin receptor antagonist in phase III development with first-in-class potential as a treatment for primary insomnia.
 
Under the terms of the agreement, GSK will receive exclusive worldwide rights to co-develop and co-commercialise almorexant.  Actelion will continue to lead the ongoing development programme and potential registration for almorexant in the first indication, primary insomnia, with GSK contributing 40 per cent of the costs.  Almorexant will also be studied in other orexin-related disorders and all costs related to these programmes will be shared equally. 
 
Actelion will receive an upfront payment of CHF 150 million (approximately £66 million) and will be eligible for additional potential milestone payments of up to CHF 415 million in regards to 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 commercialised, 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. Also, costs and profits resulting from this collaboration will be shared equally between the two companies.
 
Dr Moncef Slaoui, Chairman of Research and Development, GSK, commented, "GSK and Actelion both share the vision - based on our individual research efforts - that orexin receptor antagonists have tremendous potential. By targeting orexin, which is known to help regulate the sleep-wake cycle, these novel molecules could help to reduce or even eliminate some of the side-effects associated with current sleep treatments."
 
Jean-Paul Clozel, MD and Chief Executive Officer of Actelion commented: "Almorexant has the potential to fundamentally change the treatment of sleep disorders. GSK, with its strong track record of successful worldwide commercialisation, is the ideal partner to work with Actelion to rapidly bring this novel medicine - with the potential to restore normal physiological sleep - to insomnia patients all around the globe. In addition, this alliance allows Actelion and GSK to create significant additional value by rapidly expanding clinical development of almorexant beyond primary insomnia."
 
Collaboration to realise full potential of orexin antagonism
 
At the end of 2007, Actelion initiated Phase III development for almorexant, with the pivotal studies required for registration in the U.S. scheduled to commence later in 2008. The RESTORA (REstore normal physiological Sleep with The Orexin Receptor antagonist Almorexant) programme is evaluating the safety and efficacy of almorexant in adult and elderly patients diagnosed with primary insomnia.
 
Actelion and GSK will equally share costs and profit in key pharmaceutical markets worldwide where they will co-commercialise almorexant.  In these markets Actelion will book all sales and GSK will book its share of profit.  GSK will grant Actelion the right to assist in the commercialisation - as a paid-for sales force - of a GSK product in certain countries and for a limited period of time. In emerging markets, GSK will commercialise the product exclusively, with Actelion receiving a 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.
 
Every night, insomnia - or sleeplessness - affects or impairs an estimated 150 million patients worldwide, resulting in significant negative health consequences. Patients with insomnia tend to have higher rates of mental health problems, drug and alcohol abuse, and cardiac morbidity. In the United States alone, the direct and indirect economic costs of sleep disorders are estimated to be in the range of USD 35 billion annually. [1,2]
 
 
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Notes to the Editor:
 
About sleep disorders
In the United States alone, a 2005 National Institutes of Health (NIH) State of Science conference about chronic insomnia estimated that there were up to 80 million Americans suffering from sleeplessness, of which 25 million suffered from chronic insomnia. Insomnia has a significant health and quality-of-life impact. People with insomnia tend to have higher rates of mental health problems, drug and alcohol abuse, and cardiac morbidity.
 
About orexins and almorexant
Orexins - previously referred to as hypocretins - are proteins produced by the hypothalamus. They play an important role in controlling the sleep-wake cycle. Almorexant is the first-in-class orexin receptor antagonist in clinical development as a potential new treatment for insomnia and other central nervous system 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. It was discovered by researchers at Actelion Pharmaceuticals in 2003. Almorexant is covered by a patent application.
 
About the Phase III program RESTORA with almorexant
In December 2007, Actelion initiated the registration program RESTORA (REstore normal physiological Sleep with The Orexin Receptor antagonist Almorexant) to evaluate efficacy and safety of almorexant in both adult and elderly patients diagnosed with insomnia. The RESTORA program also includes profiling studies, for example comparing almorexant with currently used hypnotics targeting benzodiazepine receptors. The RESTORA program studies are expected to report first findings in the second half of 2009.
 
Previous studies supporting RESTORA
Prior to initiation of the RESTORA study, a proof-of-concept/dose-ranging study in patients with primary insomnia indicated that almorexant significantly improved the primary parameter of sleep efficiency (time spent sleeping while confined to bed during an eight hour period at night) measured by polysomnography (PSG) - at 400 mg, 200 mg and 100 mg in a dose-dependent manner.
 
Analysis of secondary and exploratory endpoints, for which the study was not powered, also indicated that the use of almorexant resulted in other clinically relevant improvements in important PSG-assessed sleep parameters. Almorexant was found - in a dose-dependent fashion - to decrease LPS, (significant finding at 400 mg) and to decrease WASO, (significant finding at 400 mg, 200 mg and 100 mg).
 
Almorexant increased or maintained both percentage of time spent in REM (Rapid-Eye-Movement) and non-REM sleep in a normal proportion. Almorexant also significantly improved subjective sleep variables. Treatment with almorexant was not associated with any relevant negative effects on next-day performance (assessed by fine motor testing and mean reaction time).
 
Treatment with almorexant was generally well tolerated and there were no reports of serious adverse events and no emerging safety findings. These results - presented in posters, abstracts and presentations at the World Sleep Congress 2007 in Cairns/Australia - are consistent with earlier observations made in pre-clinical and early clinical studies recently published in Nature Medicine [ 3].
 
The entry-into-human study in 70 healthy male subjects assessing tolerability, safety, pharmacokinetics and pharmacodynamics revealed that the tested doses (up to 1000 mg) were generally well tolerated and there were no safety concerns. A multiple-ascending dose (MAD) study performed in both female and male healthy subjects receiving up to 1000mg for up to six days showed similar results.
 
References
1.       National Institutes of Health (NIH) State of Science conference on chronic insomnia, 2005.
2.       EU National Health and Wellness Survey, Insomnia analysis 2006-2007.
3.       Brisbare-Roch C. et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007 Feb;13  (2):150-5
 
About GlaxoSmithKline
GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.
 
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 1700 employees focus on the discovery, development and marketing of innovative drugs for significant unmet medical needs. Actelion shares are traded on the SWX Swiss Exchange (ticker symbol: ATLN).

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