Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension

• Published in: The European respiratory journal Vol. 40; no. 4; pp. 874 - 880
• Main Authors: Simonneau, Gérald, Torbicki, Adam, Hoeper, Marius M., Delcroix, Marion, Karlócai, Kristóf, Galiè, Nazzareno, Degano, Bruno, Bonderman, Diana, Kurzyna, Marcin, Efficace, Michela, Giorgino, Ruben, Lang, Irene M.
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01.10.2012
• Subjects: Acetamides - therapeutic use; Administration, Oral; Adult; Aged; Biological and medical sciences; Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary - drug therapy; Male; Medical sciences; Middle Aged; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pyrazines - therapeutic use; Receptors, Epoprostenol; Receptors, Prostaglandin - agonists; Treatment Outcome; Vascular Resistance - drug effects; Vasodilator Agents - therapeutic use; Agonist; Prostaglandin I2; Respiratory disease; prostacyclin; Oral administration; Cardiovascular disease; randomised controlled trial; Artery; Pulmonary hypertension; Treatment; Haemodynamics; Hemodynamics; pulmonary arterial hypertension; Pneumology; Biological receptor
• DOI: 10.1183/09031936.00137511
• ISSN: 0903-1936; 1399-3003

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 pulmonary arterial hypertension (PAH). 43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the 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 end-point, and was analysed in the per protocol set first and then in 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% confidence limits -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.