Selexipag for the treatment of pulmonary arterial hypertension

Expert Opin Pharmacother. 2014 Feb;15(3):429-36. doi: 10.1517/14656566.2014.876007. Epub 2014 Jan 7.


Introduction: Selexipag is a first-in-class orally available selective non-prostanoid IP receptor agonist. This review was based on a PubMed search and focuses on the potential role of selexipag in the treatment of pulmonary arterial hypertension (PAH).

Areas covered: Selexipag is rapidly hydrolyzed to an active metabolite, ACT-333679. Both selexipag and its metabolite are highly selective for the IP receptor compared with other prostanoid receptors. This selectivity for the IP receptor offers the potential for improved tolerability with selexipag, as side effects (e.g., nausea and vomiting) that might result from activation of the other prostanoid receptors may be minimized. In addition, the selexipag metabolite has a half-life of 7.9 h, thus permitting oral dosing twice daily. Selexipag showed effects on pharmacodynamic end points obtained with right heart catheterization in a Phase II trial in patients with PAH, and is being evaluated in the ongoing Phase III trial (GRIPHON trial, NCT01106014).

Expert opinion: The signal of a beneficial effect of selexipag on disease progression may become more robust for long term under prolonged exposure. Pending the GRIPHON trial results, selexipag could provide a convenient first-line prostacyclin treatment option for patients with PAH.

Publication types

  • Review

MeSH terms

  • Acetamides / pharmacokinetics
  • Acetamides / therapeutic use*
  • Acetates / metabolism
  • Administration, Oral
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Familial Primary Pulmonary Hypertension
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / metabolism
  • Prostaglandins I / metabolism
  • Pyrazines / metabolism
  • Pyrazines / pharmacokinetics
  • Pyrazines / therapeutic use*
  • Receptors, Prostaglandin / agonists*
  • Signal Transduction


  • Acetamides
  • Acetates
  • Prostaglandins I
  • Pyrazines
  • Receptors, Prostaglandin
  • selexipag
  • (4-((5,6-diphenylpyrazin-2-yl)(isopropyl)amino)butoxy)acetic acid

Associated data