Actelion submits US FDA New Drug Application for selexipag (Uptravi) in patients with pulmonary arterial hypertension - Seite 3

This pivotal, event-driven study was designed to demonstrate a prolongation of time to the first morbidity/mortality event for selexipag compared to placebo and to evaluate the safety of the selexipag in PAH patients. All morbidity and mortality events reported by the investigators were adjudicated by an independent Critical Event Committee blinded to the study treatment.  

DOSING IN GRIPHON

Uptitration of selexipag allows each patient's maintenance dose to be individualized based on tolerability. Dosing in GRIPHON was initiated at 200 micrograms (mcg) bid and increased in steps of 200 mcg twice daily up to a maximum of 1600 mcg twice daily.

ABOUT SAFETY AND TOLERABILITY IN GRIPHON

The most common adverse events in GRIPHON that occurred with higher frequency on selexipag than placebo were in-line with those known in prostacyclin therapies; headache, diarrhea, nausea, jaw pain, vomiting, pain in extremity, myalgia, nasopharyngitis and flushing.

The proportion of patients discontinuing treatment due to adverse events was 14 percent on selexipag and 7 percent on placebo.

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 orally-available, selective prostacyclin IP receptor agonist for patients suffering from pulmonary arterial hypertension (PAH). This compound was originally discovered and synthesized by Nippon Shinyaku. 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. 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.
2. Mubarak KK. A review of prostaglandin analogs in the management of patients with pulmonary arterial hypertension. Respir Med 2010;104:9-21.Morrison et al. Selexipag: a selective prostacyclin receptor agonist that does not affect rat gastric function. J Pharmacol Exp Ther 2010;335:249-255.
3. Morrison et al. Differential effects of selexipag and prostacyclin analogs in rat pulmonary artery. J Pharmacol Exp Ther 2012;343:547-555. 
4. Simonneau G, Lang I, Torbicki A, Hoeper MM, Delcroix M, Karlocai K, Galie N. Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension Eur Respir J 2012; 40: 874-880