About Actelion's S1P1 receptor agonist program in clinical development
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
Actelion’s first-in-class selective S1P1 receptor agonist is currently investigated in a a multi center, randomized, double blind, placebo controlled, parallel group, dose finding study to evaluate the efficacy, safety, and tolerability of three doses of the compound administered for twenty-four weeks in 400 patients with relapsing-remitting multiple sclerosis (RRMS). The study is designed to assess the efficacy of this innovative compound, as compared to placebo, on magnetic resonance imaging endpoints.
Actelion's S1P1 receptor agonist in development for Psoriasis
Current status
The proof-of-concept study, with 66 patients, provided sufficient information to proceed with the first pivotal study in psoriasis.
The Phase IIa study also extended the safety information of this innovative compound, 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.
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-humans
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.
