About Selexipag
Selexipag (previously known as ACT-293987 or NS-304), originally discovered and synthesized by Nippon Shinyaku, is a long-lasting orally-available drug that is converted to the active principle, a potent non-prostanoid IP receptor agonist which exerts vasodilating effects. Selexipag has major potential as a novel treatment of pulmonary arterial hypertension.
In April 2008, Actelion and Nippon Shinyaku signed a licensing agreement, under which Actelion will be responsible for the global development and commercialization of selexipag outside Japan, and the two companies will co-develop and co-commercialize the drug in Japan.
Selexipag in development for PAH
Current status
Selexipag is currently being evaluated in the Phase III GRIPHON, (Prostacyclin (PGI2) Receptor agonist in pulmonary arterial hypertension) trial, which is enrolling patients around the world.
GRIPHON is a multicenter, double-blind, placebo-controlled morbidity/mortality trial evaluating the efficacy and safety of oral selexipag in patients with pulmonary arterial hypertension.
The primary endpoint of the trial is to demonstrate the effect of Selexipag on the time to first clinical event of morbidity or mortality in patients with PAH. This trial is being conducted under an agreed special protocol assessment (SPA) with the U.S. Food and Drug Administration.
Available clinical data
Results of the Phase II, 43-patient, placebo-controlled, double-blind study, where patients were randomized in a 3:1 ratio receiving selexipag or placebo, showed a statistically significant reduction in pulmonary vascular resistance (PVR; primary parameter for the study). The treatment effect was shown to be 30.3 percent after 17 weeks of treatment (p=0.0045). Results also showed an encouraging numerical improvement in 6-minute walk distance (6MWD), which was a secondary endpoint of this trial. Selexipag was well tolerated and the safety profile was in-line with the expected pharmacologic effect.
Data from the Phase I study indicated that multiple doses up to 1600 μg bid were well tolerated. There was no clinically relevant pharmacokinetic or pharmacodynamic interaction with warfarin.
Milestones
2010 – Positive Phase II study with selexipag presented at ATS
2009 – First patient enrolled in Phase III morbidity / mortality study
2009 – Positive Phase IIa data obtained - primary endpoint met with statistical significance
2008 – Actelion in-licensed selexipag
2008 – Phase II studies initiated
Key scientific literature
Kuwano et al (2007). NS-304, an orally available and long-acting prostacyclin receptor agonist prodrug. J Pharmacol Exp Ther 322: 1181-1188.
Kuwano et al (2008). 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 326: 691-699.
