Actelion's selective S1P1 receptor agonist moves into advanced clinical development in psoriasis

Actelion's selective S1P1 receptor agonist moves into advanced clinical development in psoriasis - Phase IIb dose-finding study in multiple sclerosis already ongoing - Roche to leave S1P1 alliance following comprehensive portfolio review and prioritization
ALLSCHWIL, SWITZERLAND - 08 December 2009 - Actelion Ltd (SIX: ATLN) announced today that the company has decided to proceed with advanced clinical development with its orally available and selective S1P1 receptor agonist (ACT-128800) in psoriasis. ACT-128800 is already in advanced clinical development for multiple sclerosis, where a dose-finding study has started recruiting patients in early October 2009.
Actelion will move forward in developing ACT-128800 in these two programs and other autoimmune indications. Basel-based Roche informed Actelion on 7 December 2009 that it does not wish to continue the S1P1 alliance, following a comprehensive portfolio review. Since the integration of the Genentech portfolio, Roche has been carrying out extensive reviews of its combined R&D portfolio.
The decision by Roche to leave the alliance results in accelerated recognition of the deferred revenues from milestones previously paid to Actelion. As of the date of termination, the amount of unrecognized revenue was USD 88.7 million, which will be recognized over the 6 months starting in December of this year.
Jean-Paul Clozel, M.D. and Chief Executive Officer of Actelion commented: "I would like to thank Roche for their contribution and their expertise in progressing this program to the present stage. Today, Actelion has all the assets at hand - medical know-how, global development, global sales and marketing capabilities and strong cash flow - to successfully develop and commercialize our promising selective S1P1 receptor agonist in several indications."
Jean-Paul Clozel concluded: "I am convinced that Actelion's selective S1P1 receptor agonist, an oral and rapidly reversible immunotherapy - has the potential to improve therapy for patients. Especially, I expect that our selective S1P1 receptor agonist could have a wider safety margin compared to other therapies currently available or in development, whether they are long-acting biological immunosuppressive or other oral approaches." 
Actelion's decision to advance its selective S1P1 receptor agonist for the treatment of psoriasis is based on a recently concluded Phase IIa proof-of-concept study. While this short term study did not reach statistical significance, sufficient information was obtained to proceed with a first pivotal study in psoriasis.
The Phase IIa study also extended the safety information of ACT-128800, previously established in healthy volunteers, to a larger group of psoriasis patients for up to six weeks of treatment. Full study results will become available through future presentation at major scientific meetings and subsequent scientific publication.
In multiple sclerosis, Actelion is currently undertaking a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study to evaluate the efficacy, safety, and tolerability of three doses of Actelion's S1P1 receptor agonist administered for twenty-four weeks in 400 patients with relapsing-remitting multiple sclerosis (RRMS). The study is designed to assess the efficacy of ACT-128800, as compared to placebo, on magnetic resonance imaging endpoints.
Notes to the editor
About selective S1P receptor agonism
Sphingosine-1-phosphate (S1P) is a phospholipid released by erythrocytes, platelets, mast cells and other cells. It is currently established [1,2] that S1P stimulates at least five different G-protein coupled receptors (GPCRs): S1P1,2,3,4, and 5. Activation of these GPCRs mediates a complex variety of biological responses, such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction and heart rate modulation.
About Actelion and selective S1P1 agonists
Actelion's efforts in the field of selective S1P1 receptor agonists started in 1999 by focusing on GPCRs found on the endothelium, the inner lining of blood vessels. The result of these research efforts is Actelion's orally active selective S1P1 receptor agonist, ACT-128800. The company also has a comprehensive research effort ongoing to discover and develop other S1P1 receptor agonists and antagonists.
About ACT-128800
ACT-128800 is a potent, orally active, selective sphingosine 1-phosphate receptor 1 (S1P1) agonist. ACT-128800 blocks the egress of lymphocytes from lymphoid organs and thus reduces the availability of circulating effector T cells that can invade target organs. This pharmacodynamic effect is sustained with continued daily oral dosing, but is rapidly reversible upon drug discontinuation. ACT-128800 is therefore considered a promising new oral agent for the treatment of a variety of autoimmune disorders.
About the former Actelion / Roche S1P1 alliance
Actelion and Roche entered into an exclusive worldwide collaboration in July 2006 to jointly develop and commercialize Actelion's selective S1P1 receptor agonists. Upfront and milestone payments totaling USD 105 million have been received by Actelion under the collaboration contract, and have been recognized over the expected clinical development time for ACT-128800. Following a comprehensive portfolio review, Roche has decided to prioritize its other projects in the area of autoimmune disorders. Since the integration of the Genentech portfolio, Roche has been carrying out extensive reviews of its combined R&D portfolio. As of the date of termination, the amount of unrecognized revenue was USD 88.7 million, which will be recognized in Actelion's Profit and Loss Statements over the 6 months starting December 2009.
About autoimmune disorders
Autoimmune disorders are diseases caused by the body producing an immune response against its own tissues. The cause of autoimmune disorders is unknown. Some of the most common types of autoimmune disorders include psoriasis, rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. These disorders affect millions of people worldwide.
About Psoriasis
Psoriasis is a chronic, relapsing, inflammatory and immune-mediated skin disease affecting about 1-3% of the population worldwide. Plaque psoriasis is the most common form of psoriasis constituting ~ 85% of cases [1]. The most characteristic skin lesions of chronic plaque psoriasis are sharply demarcated erythematous plaques, covered by silvery white scales, which most commonly occur on the elbows, knees, scalp, umbilicus, and lumbar area. Children, adolescents, and adults are affected. The causes are not known, however, both environmental and genetic causes have been implicated. Current research suggests that the inflammatory mechanisms are immune based [2,3].
About Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disorder of the central nervous system (CNS) and is the most common cause of progressive neurological disability in young adults [4,5]. MS with its mechanism of inflammation, demyelination, and neurodegeneration is characterized by heterogeneous clinical expression, an unpredictable course and a variable prognosis. MS results from a cascade of events involving an activation of the immune system, acute focal inflammatory demyelinating lesions with limited remyelination, and axonal loss with limited remyelination, culminating in chronic multifocal sclerotic plaques in brain and spinal cord. The large variety of symptoms and signs of MS result from axonal demyelization or axon loss which leads to the slowing or blockade of axonal conduction at diverse affected sites of the brain and spinal cord. Repeated episodes of disease activity may lead to progressive loss of neurological function.
The incidence of MS is about 7 cases per 100,000 persons per year [4] and although the etiology of MS is still unknown, the prevalence rate varies between ethnic origins and geographical latitudes, ranging from 50-120 per 100,000 [4]. It is widely accepted that it is an immune-mediated, demyelinating disease precipitated by unknown environmental factors in genetically susceptible people.
1.       Naldi L, Gambini D. The clinical spectrum of psoriasis. Clin Dermatol 2007;25:510-518.
2.       Nickoloff BJ, Quin JZ, Nestle FO. Immunopathogenesis of psoriasis. Clinic Rev Allerg Immunol 2007;33:45-56.
3.       Ghoreschi K, Weigert C, Röcken M. Immunopathogenesis and role of T cells in psoriasis. Clin Dermatol 2007;25:547-580.
4.       Compston A, Coles A. Multiple sclerosis. Lancet 2002;359:1221-31.
5.       Compston A, Coles A. Multiple sclerosis. Lancet 2008;372:1502-18.
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 2'200 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