OREANDA-NEWS. Actelion Ltd (SIX: ATLN) announced today that it is accelerating its clinical development efforts in the field of immunological disorders, following a broad scientific, medical and commercial evaluation of a series of its selective S1P1 receptor modulators, discovered in-house.

Actelion has initiated Phase III development with ponesimod, its lead compound, in patients suffering from relapsing multiple sclerosis, with patient enrollment expected imminently.

In parallel, Actelion will also initiate a Phase II study with ponesimod in patients suffering from chronic graft versus host disease. In addition, a second selective S1P1 receptor modulator will advance into Phase II clinical development in patients with systemic lupus erythematosus.

Jean-Paul Clozel, M.D. and Chief Executive Officer commented: "Our efforts in the field of immunology have reached the necessary maturity to warrant fully-fledged clinical investigation. We have a thorough understanding of what selective S1P1 receptor modulators can bring to the clinic and have matched our compounds with the appropriate indication. We have carried out extensive groundwork and benefited from Health Authority input to design the optimal clinical program, which balances clinical risk, investment, medical need and commercial opportunity."

Jean-Paul continued: "Our ongoing success in the field of PAH is enabling us to pursue the second element of our strategy and take action now to build an additional specialty franchise in the field of immunology. Our confidence in our portfolio means we can take this step while maintaining our commitment to optimize profitability."

ABOUT PONESIMOD

Ponesimod is an orally active, selective sphingosine-1-phosphate receptor 1 (S1P1) immunomodulator. Ponesimod prevents lymphocytes from leaving lymph nodes, thereby reducing circulating blood lymphocyte counts and preventing infiltration of lymphocytes into target tissues. The lymphocyte count reduction is rapid, dose-responsive, is sustained with continued dosing and quickly reversed upon discontinuation. Initial results suggest that ponesimod does not cause lymphotoxicity by destroying lymphocytes or interfering with their cellular function. Other blood cells e.g. cells of the innate immune system are largely unaffected. Ponesimod is therefore considered a promising new oral agent for the treatment of a variety of autoimmune disorders.

ABOUT MULTIPLE SCLEROSIS

Multiple sclerosis is an autoimmune disorder of the central nervous system and is the most common cause of progressive neurological disability in young adults. It is a disease caused by a cascade of events involving an activation of the immune system, acute focal inflammatory demyelinating lesions with limited remyelination and axonal loss, culminating in chronic multifocal sclerotic plaques in the brain and spinal cord.

Patients suffering from multiple sclerosis experience a heterogeneous collection of clinical symptoms, an unpredictable course and a variable prognosis. A large variety of symptoms and signs of multiple sclerosis result from axonal demyelination and axonal loss, with a corresponding slowing or blockade of axonal conduction at affected sites of the brain and spinal cord. Repeated episodes of disease activity may lead to a progressive loss of neurological function.

The incidence of multiple sclerosis is about 7 cases per 100,000 persons per year and, although the etiology of multiple sclerosis is still unknown, the prevalence rate varies between ethnic origins and geographical latitudes, ranging from 50 to 120 per 100,000. It is widely accepted that it is an immune-mediated, demyelinating disease precipitated by unknown environmental factors in genetically susceptible people.

ABOUT CHRONIC GRAFT VS. HOST DISEASE

Chronic graft vs. host disease is a pleomorphic syndrome with autoimmune-like features. Chronic graft vs. host disease is the most serious and common long-term complication of allogeneic hematopoietic stem cell transplantation representing a leading cause of late death in these patients.

The disease which has a median time to onset of 4 to 6 months after transplantation [5], can affect multiple sites, including the skin and subcutaneous connective tissues, lacrimal and salivary glands, oral mucosa, lungs, esophagus, joints, gastrointestinal tract and liver.