Selexipag, originally discovered and synthesized by Nippon Shinyaku, is a first-in-class, potent, orally available, selective 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.

Current status
Selexipag is being evaluated in the Phase III GRIPHON, (Prostacyclin (PGI₂) Receptor agonist in pulmonary arterial hypertension) trial. GRIPHON is a multicenter, double-blind, placebo-controlled trial evaluating the efficacy and safety of oral selexipag in patients with pulmonary arterial hypertension.

GRIPHON is currently enrolling a target of 1,150 patients around the world. The primary endpoint of the trial is to demonstrate the effect of selexipag on the time to first clinical event of morbidity or mortality.

Given current recruitment rates, the target enrollment is predicted to be completed by the end of 2012. Consequently, final results are expected to be available mid-2014. There will be an interim analysis for efficacy and futility at around two thirds of the total number of required events.

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 on top of PDE5 and/or ERA, 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.

Selexipag was well tolerated in healthy subjects exposed to the drug in the Phase I program. No clinically relevant or significant safety issues have emerged to date in healthy subjects exposed to selexipag in the Phase I program.

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

Morrison K, et al. J Pharmacol Exp Ther 2010;335:249–55.

Simonneau et al., Am J Respir Crit Care Med. 2010;181:A2515.