Eur Respir J. 2012 Feb 23. [Epub ahead of print]

Selexipag, an oral, selective IP receptor agonist for the treatment of pulmonary arterial hypertension.

Simonneau G, Torbicki A, Hoeper MM, Delcroix M, Karlócai K, Galiè N, Degano B, Bonderman D, Kurzyna M, Efficace M, Giorgino R, Lang IM.

Dept of Pneumology, Clamart, France.

Abstract

In this Phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for PAH.Forty-three adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one: selexipag to placebo. Dosage was up-titrated in 200 μg increments from 200 μg twice daily on Day 1 to maximum tolerated dose by Day 35 (maximum allowed dose of 800 μg twice daily). Change in pulmonary vascular resistance at Week 17 expressed as a percentage of the baseline value was the primary efficacy endpoint; analysed on the per protocol set first and then on the all-treated set to assess robustness of results.A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% CL: -44.7, -12.2; p=0.0045, Wilcoxon rank-sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect.Our results encourage the further investigation of selexipag for the treatment of PAH.

PMID: 22362844