About Actelion's selective S1P1 receptor agonist
Actelion has identified novel small molecules for clinical development on the basis of their S1P1 receptor selectivity. These molecules also have high potency and a favorable pharmacokinetic profile after oral dosing, resulting in a substantial and rapidly reversible depletion of circulating lymphocytes. They are effective in animal models of T cell mediated inflammation.
Actelion's selective S1P1 receptor agonists are potential therapeutic agents for immune disorders in which activated T cells play a critical role. In these pathological situations, traditional immunosuppressants have a high potential for toxicity, slow reversibility, and may increase the risk of infection or malignancy.
Actelion's selective S1P1 receptor agonist is currently in development, as an immunomodulator with the potential for once-a-day oral dosing, for multiple autoimmune disorders.
Actelion's S1P1 receptor agonist in development for multiple sclerosis
Current status
Following a successful Phase I program, Actelion's first-in-class selective S1P1 receptor agonist is currently investigated in a Phase IIb dose-response study in patients with multiple sclerosis. The study has enrolled more than half of the 400 planned patients and consequently results are expected in the second half of 2011.
Actelion's S1P1 receptor agonist in development for psoriasis
Current status
Actelion has advanced its selective S1P1 receptor agonist for the treatment of psoriasis based on a Phase IIa proof-of-concept study. While this short term study did not reach statistical significance, sufficient information was obtained to proceed in psoriasis.
A large Phase II study will be initiated later this year.
Available clinical data
Given the marked lymphocyte lowering effects, the Phase I data support further exploration of Actelion’s S1P1 receptor agonist in patients.
Milestones
2009 – Initiation of dose-finding study in multiple sclerosis
2008 – Initiation of proof of concept study in Psoriasis
2006 – Entry-into-man
2004 – Preclinical development initiated
Key scientific literature
Waubant E. Emerging therapies for MS.Rev Neurol (Paris). 163(6-7):688-96; 2007.
Brinkmann V. Sphingosine 1-phosphate receptors in health and disease: mechanistic insights from gene deletion studies and reverse pharmacology. Pharmacol Ther. 115(1):84-105; 2007.
Rosen H. et al. Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol. 28(3):102-7; 2007.
Doggrell SA. Is fingolimod an advancement in the treatment of multiple sclerosis? Expert Opin Pharmacother. 8(3):383-6; 2007.
Kappos L. et al. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 355(11):1124-40; 2006.
