Uptravi (selexipag), originally discovered and synthesized by Nippon Shinyaku, is the only approved oral selective IP receptor agonist targeting the prostacyclin pathway in PAH.


Current Indications

In the US, Uptravi is indicated for the treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms. Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%).

In Europe, Uptravi is indicated for the long-term treatment of PAH in adult patients with WHO functional class II-III, either as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies. Efficacy has been shown in a PAH population including idiopathic and heritable PAH, PAH associated with connective tissue disorders, and PAH associated with corrected simple congenital heart disease.

As with other therapies targeting the prostacyclin pathway, hyperthyroidism has been observed with Uptravi. If there are any signs of pulmonary edema, the possibility of pulmonary veno-occlusive disease should be considered and, if confirmed, Uptravi should be discontinued. Other adverse events observed with Uptravi usage were similar in nature to those expected with prostacyclin receptor agonists.


Uptravi is commercially available in 9 countries, including the US (since January 2016) and Germany (since June 2016).

Market authorization has been received in Australia, Canada, the European Union, Japan, New Zealand, South Korea, Switzerland and the US.
Submission of the registration dossier to other health authorities is ongoing.

For current information, visit www.actelion.com

Available Clinical Data

GRIPHON, a global, pivotal Phase III 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 selexipag in PAH patients.

A total of 1’156 patients were randomized to receive placebo or selexipag. Utilizing a dosing scheme that titrated patients up to their individualized doses, dosing in GRIPHON was initiated at 200 micrograms (mcg) twice daily (b.i.d) and increased weekly in steps of 200 mcg up to a maximum of 1600 mcg b.i.d. If patients were unable to tolerate a dose, the dose was reduced to previously tolerated dose. A primary endpoint event occurred in 397 patients – 41.6% of those in the placebo group and 27.0% of those in the selexipag group (hazard ratio in the selexipag group as compared with the placebo group, 0.60; 99% confidence interval, 0.46 to 0.78; P<0.0001). Disease progression and hospitalization accounted for 81.9% of the events. At baseline, 80% of patients were receiving oral medication specific for PAH: either an ERA, a PDE-5 inhibitor, or a combination of the two. The effect of selexipag with respect to the primary endpoint was similar in the subgroup of patients who were not receiving treatment for the disease at baseline and in the subgroup of patients who were already receiving PAH-specific treatment at baseline (including those who were receiving a combination of both ERA and PDE-5 inhibitor). Adverse reactions occurring more frequently on Uptravi compared to placebo by ≥3%, over the course of the study, were headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, flushing, arthralgia, anemia, decreased appetite and rash. These adverse reactions were more frequent during the dose titration phase. Hyperthyroidism was observed in 1% (n=8) of patients on selexipag and in none of the patients on placebo.


  • Sitbon O et al. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med 2015; 373:2522-33.
  • Tetsuo Asaki et al. Selexipag: an oral and selective IP prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension. J. Med. Chem., 2015, 58 (18), pp 7128–7137.
  • Morrison et al. Differential effects of selexipag and prostacyclin analogs in rat pulmonary artery. J Pharmacol Exp Ther 2012;343:547-555.
  • 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.
  • 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.



Please note that the information contained in this section of the website is not intended for US residents. Please visit our US webpage.

Please note that the information contained in this section of the website is not intended for US residents. Please visit our US webpage.