Actelion provides update on Phase III GRIPHON study with selexipag in pulmonary arterial hypertension - Study continues - Seite 3

Despite these advances in PAH, survival rates are unacceptably low and PAH remains incurable.

ABOUT PROSTACYCLIN

Prostacyclin and prostaglandins are types of prostanoids. Endothelial cells produce several vasoactive chemical factors, among them prostacyclin (PGI₂), which induce vasodilation of blood vessels and inhibit smooth muscle cell proliferation and platelet aggregation. The peptide endothelin is also produced by the endothelium, and is a potent constrictor of blood vessels and promotes cell proliferation. In a normal healthy state, prostacyclin helps counter-balance the actions of endothelin. In certain disease conditions, however, production of prostacyclin by the endothelium is impaired, allowing the deleterious effects of excessive levels of endothelin to predominate.

ABOUT PROSTACYCLIN RECEPTOR AGONISM

The IP receptor (PGI₂ (prostacyclin) receptor) is one of 5 types of prostanoid receptor available to prostanoid replacement therapies. Prostacyclin activates the IP receptor inducing vasodilation and inhibiting proliferation of vascular smooth muscle cells. With selective IP receptor agonism, the risk of side effects mediated by activation of other prostanoid receptors may be minimized. 

Actelion is developing a first-in-class, orally available, selective IP receptor agonist that mimics the actions of endogenous prostacyclin for the treatment of PAH.

ABOUT THE ACTELION / NIPPON SHINYAKU ALLIANCE

Actelion and Nippon Shinyaku entered into an exclusive worldwide alliance in April 2008 to collaborate on selexipag, a first-in-class orally-available, selective IP receptor agonist for patients suffering from pulmonary arterial hypertension (PAH). This compound was originally discovered and synthesized by Nippon Shinyaku. Phase II evaluation has been completed, and a Phase III program in PAH patients has been initiated. Actelion is responsible for global development and commercialization of selexipag outside Japan, while the two companies will co-develop and co-commercialize in Japan. Nippon Shinyaku will receive milestone payments based on development stage and sales milestones as well as royalties on any sales of selexipag. 

References

1. Kuwano et al. NS-304, an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 2007;322:1181-1188.
    
2. Kuwano et al. A long-acting and highly selective prostacyclin receptor agonist prodrug, NS-304, ameliorates rat pulmonary hypertension with unique relaxant responses of its active form MRE-269 on rat pulmonary artery. J Pharmacol Exp Ther 2008;326:691-699.