Selexipag (ACT-293987) in Pulmonary Arterial Hypertension

Summary

The AC-065A302 (GRIPHON) study is an event-driven Phase 3 study to demonstrate the effect of selexipag on time to first morbidity or mortality event in patients with pulmonary arterial hypertension.

Timeline

Start

2009-12-01

Primary completion

2014-04-01

Completion

2014-10-01

Outcome

Met primary endpoint

registry analysis (unspecified test); Selexipag vs Placebo; p <0.0001; Hazard Ratio (HR) 0.6 (99% CI 0.46 to 0.78); Log Rank; note: one-sided p-value NCT01106014 ↗

paper the risk of the primary composite end point of death or a complication related to pulmonary arterial hypertension was significantly lower with selexipag than with placebo. PMID 26699168 ↗

Publications

• Results Sitbon O, Channick R, Chin KM, Frey A, Gaine S, Galie N, Ghofrani HA, Hoeper MM, Lang IM, Preiss R, Rubin LJ, Di Scala L, Tapson V, Adzerikho I, Liu J, Moiseeva O, Zeng X, Simonneau G, McLaughlin VV; GRIPHON Investigators. Selexipag for the Treatment of Pulmonary Arterial Hypertension. N Engl J Med. 2015 Dec 24;373(26):2522-33. doi: 10.1056/NEJMoa1503184.
• Benza RL, Chin KM, Gaine S, Galie N, Hoeper MM, Lang IM, McLaughlin VV, Sitbon O, Doad G, Yen J, Tang X, Tapson V. Changes in REVEAL Lite 2 risk status are associated with long-term outcomes in patients with pulmonary arterial hypertension: A post-hoc analysis of the GRIPHON study. J Heart Lung Transplant. 2024 Dec;43(12):1998-2007. doi: 10.1016/j.healun.2024.08.019. Epub 2024 Aug 31.
• Galie N, Gaine S, Channick R, Coghlan JG, Hoeper MM, Lang IM, McLaughlin VV, Lassen C, Rubin LJ, Hsu Schmitz SF, Sitbon O, Tapson VF, Chin KM. Long-Term Survival, Safety and Tolerability with Selexipag in Patients with Pulmonary Arterial Hypertension: Results from GRIPHON and its Open-Label Extension. Adv Ther. 2022 Jan;39(1):796-810. doi: 10.1007/s12325-021-01898-1. Epub 2021 Oct 30.
• Gaine S, Sitbon O, Channick RN, Chin KM, Sauter R, Galie N, Hoeper MM, McLaughlin VV, Preiss R, Rubin LJ, Simonneau G, Tapson V, Ghofrani HA, Lang I. Relationship Between Time From Diagnosis and Morbidity/Mortality in Pulmonary Arterial Hypertension: Results From the Phase III GRIPHON Study. Chest. 2021 Jul;160(1):277-286. doi: 10.1016/j.chest.2021.01.066. Epub 2021 Feb 3.
• Chin KM, Rubin LJ, Channick R, Di Scala L, Gaine S, Galie N, Ghofrani HA, Hoeper MM, Lang IM, McLaughlin VV, Preiss R, Simonneau G, Sitbon O, Tapson VF. Association of N-Terminal Pro Brain Natriuretic Peptide and Long-Term Outcome in Patients With Pulmonary Arterial Hypertension. Circulation. 2019 May 21;139(21):2440-2450. doi: 10.1161/CIRCULATIONAHA.118.039360.
• McLaughlin VV, Hoeper MM, Channick RN, Chin KM, Delcroix M, Gaine S, Ghofrani HA, Jansa P, Lang IM, Mehta S, Pulido T, Sastry BKS, Simonneau G, Sitbon O, Souza R, Torbicki A, Tapson VF, Perchenet L, Preiss R, Verweij P, Rubin LJ, Galie N. Pulmonary Arterial Hypertension-Related Morbidity Is Prognostic for Mortality. J Am Coll Cardiol. 2018 Feb 20;71(7):752-763. doi: 10.1016/j.jacc.2017.12.010.
• Coghlan JG, Channick R, Chin K, Di Scala L, Galie N, Ghofrani HA, Hoeper MM, Lang IM, McLaughlin V, Preiss R, Rubin LJ, Simonneau G, Sitbon O, Tapson VF, Gaine S. Targeting the Prostacyclin Pathway with Selexipag in Patients with Pulmonary Arterial Hypertension Receiving Double Combination Therapy: Insights from the Randomized Controlled GRIPHON Study. Am J Cardiovasc Drugs. 2018 Feb;18(1):37-47. doi: 10.1007/s40256-017-0262-z.
• Gaine S, Chin K, Coghlan G, Channick R, Di Scala L, Galie N, Ghofrani HA, Lang IM, McLaughlin V, Preiss R, Rubin LJ, Simonneau G, Sitbon O, Tapson VF, Hoeper MM. Selexipag for the treatment of connective tissue disease-associated pulmonary arterial hypertension. Eur Respir J. 2017 Aug 17;50(2):1602493. doi: 10.1183/13993003.02493-2016. Print 2017 Aug.
• Krause A, Machacek M, Lott D, Hurst N, Bruderer S, Dingemanse J. Population Modeling of Selexipag Pharmacokinetics and Clinical Response Parameters in Patients With Pulmonary Arterial Hypertension. CPT Pharmacometrics Syst Pharmacol. 2017 Jul;6(7):477-485. doi: 10.1002/psp4.12202. Epub 2017 May 27.
• Skoro-Sajer N, Lang IM. 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.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Selexipag	Small molecule	200 ug	Oral
Subject	Selexipag	Small molecule	400 ug	Oral
Subject	Selexipag	Small molecule	600 ug	Oral
Subject	Selexipag	Small molecule	800 ug	Oral
Subject	Selexipag	Small molecule	1000 ug	Oral
Subject	Selexipag	Small molecule	1200 ug	Oral
Subject	Selexipag	Small molecule	1400 ug	Oral
Subject	Selexipag	Small molecule	1600 ug	Oral

Indications