An evaluation of selexipag for the treatment of pulmonary hypertension

ABSTRACT

Introduction

Selexipag is a first-in-class, oral, long-acting, selective, non-prostanoid agonist of the prostacyclin receptor (IP receptor), indicated for the treatment of symptomatic adult pulmonary arterial hypertension (PAH). It was designed with the objective to surpass the inconveniences associated with standard prostanoid therapy, presenting fewer adverse effects and comparable hemodynamic benefits.

Areas covered

This review describes the pharmacologic properties of selexipag and presents the clinical trials that have been completed or are currently ongoing regarding its clinical efficacy, safety, and tolerability. The pivotal GRIPHON study is extensively presented.

Expert opinion

Selexipag is the first IP receptor to reduce the morbidity/mortality composite endpoint of the GRIPHON study, a large, randomized, placebo-controlled study. The TRITON study failed to demonstrate a clear benefit of initial triple oral therapy including selexipag compared to initial double oral therapy. Current guidelines do not provide definitive recommendations regarding the place of selexipag in the treatment algorithm of PAH. Finally, the possibility of transition between the several drugs acting in the prostacyclin pathway, and the potential role of selexipag in chronic thromboembolic pulmonary hypertension and pediatric PAH is currently being examined, possibly expanding its future use.

KEYWORDS:

• ACT-293,987
• MRE-269
• selexipag
• prostacyclin
• pulmonary arterial hypertension

Article highlights

• Oral selexipag represents a first-in-class, long-acting, selective, non-prostanoid agonist of the prostacyclin receptor (IP receptor).

• The hallmark study that evaluated the efficacy of oral selexipag for the treatment of PAH is the GRIPHON trial, a randomized, double-blind, global, multicenter, placebo-controlled, event-driven trial with the largest population included in the history of PAH trials (n = 1156). The composite of the time to first event of all-cause death or a PAH-associated complication constituted the primary endpoint. In the selexipag group, a 40% reduction of time to first event was achieved [99% confidence interval (ci): 22 to 54%; two-sided log-rank p < 0.0001], with the effect being driven by the reduction of disease progression and hospitalization events.

• The TRITON trial failed to show a clear benefit of selexipag as a third agent in an upfront triple combination approach.

• Further studies are also expected to yield results regarding the clinical efficacy of selexipag in pediatric PAH and inoperable or persistent CTEPH.

Declaration of interest

A Boutou declares having received honoraria or lectures from Chiesi Farmaceutici and Elpen Hellas. She was also the recipient of a European Respiratory Society Short-Term Research Fellowship in 2013. G Pitsiou meanwhile reports receiving honoraria for lectures from Actelion-Janssen, Greece, Merck Sharp and Dohme, GlaxoSmithKline and Bayer Healthcare. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.