About Actelion's CRTH2 receptor antagonist
Actelion's CRTH2 receptor antagonist blocks the effects of prostaglandin D2 (PGD2) on inflammation and, as a consequence, the amplification and maintenance of allergic reactions. It targets allergic inflammation at the beginning of the cascade, with potential to be used as controller therapy in both asthma and/or allergic rhinitis, as well as in multiple potential indications that are based on allergic inflammation.
Actelion's CRTH2 receptor antagonist in development for asthma
Current status
Positive data have been obtained in a proof-of-mechanism study with Actelion’s orally active CRTH2 receptor antagonist in mild asthma. In preclinical studies, this compound inhibited migration and activation of fundamental cell types involved in allergic inflammation. In the 18-patient crossover double-blind placebo-controlled study, the primary endpoint (FEV1) was met, and the compound was well tolerated.
Plans for Phase II dose-ranging studies in both asthma and allergic rhinitis are on track for initiation in the second half of 2010.
Available clinical data
In Phase I studies, the compound was well tolerated and showed an appropriate pharmacological profile.
Milestones
2009 – Positive proof-of-mechanism - primary endpoint met with statistical significance
2008 – Phase II proof-of-mechanism study initiated
2007 – Entry-into-mans study initiated
2006 – Preclinical development initiated
Key scientific literature
Pettipher R. Review: The roles of the prostaglandin D2 receptors DP1 and CRTH2 in promoting allergic responses. Brit. J. Pharmacol. 1-9; 2007
Tanaka K., et al. Effects og prostaglandin D2 on helper T cell functions. Biochem & Biophys Res Coms. 316, 1009-14; 2004.
Iwasaki M., et al. Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper cells in patients with atopic dermatitis. J. Invest. Dermatol. 119:609-16; 2002.
Hirai H., et al. Prostaglandin D2 selectivity induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J. Exp. Med 193(2) 255-261; 2001.
Gervais F., et al. Selective modulation of chemkinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP. J allergy clin immunol 108 (6), 982-8; 2001.
