Selexipag: A Review in Pulmonary Arterial Hypertension

Sean T Duggan, Susan J Keam, Celeste B Burness
American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions 2017, 17 (1): 73-80
Selexipag (Uptravi® ) is an orally active, first-in-class, selective prostacyclin IP receptor agonist. Selexipag was approved recently in the EU for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class (FC) II or III as combination therapy in patients insufficiently controlled with an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor or as monotherapy in patients who are not candidates for these therapies, and in the USA for the treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. Selexipag (200-1600 μg twice daily, as tolerated) significantly reduced the risk of the primary composite endpoint of all-cause death or a complication related to PAH (whichever happened first) versus placebo in patients with PAH (mainly WHO FC II or III) in the large, randomized, placebo-controlled GRIPHON study. The treatment effect was largely driven by significant reductions in disease progression and hospitalization for PAH. However, selexipag did not significantly reduce all-cause mortality. Additionally, the observed treatment effect was consistent in a broad range of prespecified subgroups, including treatment-naïve patients and those patients who were already receiving PAH-specific treatment at baseline. Exercise capacity was also improved with selexipag versus placebo. Selexipag was generally well tolerated, with an adverse event profile consistent with other therapies targeting the prostacyclin pathway. Thus, selexipag extends the treatment options available in patients with PAH.


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