Pharmacological characteristics and clinical study results of Selexipag (Uptravi^® tablets), a selective prostacyclin receptor agonist

Abstract

Selexipag (Uptravi^® tablets) is a novel prostacyclin receptor (IP receptor) agonist designed and synthesized at Nippon Shinyaku Co., Ltd., and approved for the treatment of pulmonary arterial hypertension (PAH). Selexipag is converted to MRE-269 in vivo, and the plasma concentration of MRE-269 is maintained at a therapeutic level for a long time. MRE-269 has selective IP receptor agonist activity and exerts vasodilatory and anti-proliferative effects on pulmonary arterial smooth muscle cells. In a study to investigate its vasodilatory effect in isolated rat pulmonary arteries, MRE-269 showed potent vasodilatory effects not only in extralobar but also in small intralobar pulmonary arteries. In a Sugen 5416/hypoxia rat model of PAH, selexipag significantly improved pulmonary artery obstruction, decreased right ventricular systolic pressure, decreased right ventricular hypertrophy and improved survival rate. In a phase II clinical trial for treatment with PAH conducted in Europe, selexipag showed good tolerability with promising efficacy. In an open-label phase II study in 37 patients with PAH in Japan, selexipag significantly decreased pulmonary vascular resistance compared with baseline. In the GRIPHON (Prostacyclin (PGI₂) Receptor agonist In Pulmonary arterial HypertensiON) study in 1156 patients with PAH, the largest outcome study ever conducted in PAH, the selexipag treatment group showed a significant reduction in the risk of the primary composite endpoint of death or a complication related to PAH compared with placebo. Selexipag has been shown in clinical trials to prevent the progression of PAH, and is expected to contribute to the treatment of patients with PAH.