<p>Selexipag in the management of pulmonary arterial hypertension: an update</p>

Abstract

Selexipag is a compound that was designed to overcome the issues associated with oral administration of prostanoid compounds, beraprost and treprostinil in the treatment of pulmonary hypertension (PAH). As a selective IP agonist, it was designed to avoid the off-target prostanoid effects especially in the gastrointestinal system. To place this compound in context, this paper briefly reviews the efficacy, tolerability, and safety of subcutaneous, inhaled, and oral prostanoid preparations and comparesthemto selexipag. Selexipag is the first agent targeting a prostanoid receptor where a reduction in the primary efficacy morbidity/mortality composite end-point has been demonstrated. While safety outcomes favor selexipag over placebo, tolerability issues remain. Efficacy in terms of improvement in effort tolerance, hemodynamic and mortality benefit is less than seen with IV therapy. This is the first prostanoid demonstrated in a clinical trial to have added benefit in those on background double combination therapy and the first non IV prostanoid to demonstrate outcome benefit in the connective tissue disease (CTD) population in a randomized controlled trial.

Risk Stratification of Patients with Pulmonary Arterial Hypertension: The Role of Echocardiography

“…This is important from a clinical standpoint since the management of patients with intermediate risk is not straightforward, unlike that of patients with low-risk who need no further change in therapy or those with high-risk who obviously require more aggressive interventions, such as parenteral therapy or lung transplantation referral [ 4 , 30 ]. Therapeutic options for patients who remain in the intermediate-risk category despite dual oral combination therapy with a PDE5-I and an ERA include adding selexipag [ 31 , 32 ], switching from PDE5-I to riociguat [ 33 , 34 , 35 ], initiating parenteral prostanoids [ 12 ] and lung transplantation referral [ 12 ]. Based on this, we believe that the further risk stratification of patients in the intermediate-risk category may help clinicians decide how aggressive subsequent interventions should be.…”

The &lt;i&gt;in Vitro&lt;/i&gt; Characterisation of the Effect of Selexipag on Small Human Pulmonary Arteries

“…We have shown that murine data can be extrapolated into research involving human tissue with regards to selexipag usage. Although, current data seems to suggest that the distribution of receptors and sensitivity to pre-constriction agents may vary among species, prostacyclin analogues are known to evoke similar IP receptor activation in both humans and rats [27]. Selexipag has already been used in clinical trials, the GRIPHON study was a phase 3 double-blinded RCT that looked at the effect of selexipag compared to placebo in 1156 patients with PAH.…”

Newly Developed Prodrugs and Prodrugs in Development; an Insight of the Recent Years

“…Current trials focus on the use of selexipag in children with pulmonary arterial hypertension NCT03492177, and patients with chronic thromboembolic pulmonary hypertension NCT03689244. Preliminary results of trials which have published the outcomes of their trials show that selexipag is tolerable and pharmacokinetically and clinically effective [8].…”