Selexipag
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Selexipag
- Selexipag: From Pulmonary Arterial Hypertension to Pulmonary Arterial Hypertension Associated with Congenital Heart Disease
Selexipag: From Pulmonary Arterial Hypertension to Pulmonary Arterial Hypertension Associated with Congenital Heart Disease
One-Sentence Summary
Selexipag is an oral selective prostacyclin (IP) receptor agonist originally approved for pulmonary arterial hypertension (PAH), WHO Group 1. The TxGNN model predicts it may be effective for Pulmonary Arterial Hypertension Associated with Congenital Heart Disease (CHD-PAH), with 2 clinical trials and 15 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Pulmonary Arterial Hypertension (WHO Group 1) — inferred from repurposing rationale; no structured original-indication text available |
| Predicted New Indication | Pulmonary Arterial Hypertension Associated with Congenital Heart Disease |
| TxGNN Prediction Score | 98.03% |
| Evidence Level | L2 |
| Taiwan Market Status | Not Marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, Selexipag is an oral selective prostacyclin (IP) receptor agonist; its efficacy in pulmonary arterial hypertension has been established, and mechanistically it may be applicable to pulmonary arterial hypertension associated with congenital heart disease.
CHD-PAH is one of the recognized WHO Group 1 PAH etiological subtypes. It shares the same underlying pulmonary vascular remodeling process and IP receptor signaling pathway as the original approved PAH indication, making this a natural extension within the same disease spectrum rather than a mechanistically distant repurposing candidate.
This is further supported by the fact that CHD-PAH patients (including post-defect-correction and Eisenmenger syndrome subgroups) were included as a pre-specified subgroup in the pivotal GRIPHON Phase 3 RCT, and a dedicated Phase 4 study evaluating right-ventricular remodeling in this population has been conducted, indicating the drug class is already used clinically in this etiological subtype.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04435782 | Phase 4 | Terminated | 9 | Single-arm study assessing selexipag’s effect on right ventricular (RV) function/remodeling in PAH via cardiac MRI; terminated early due to under-enrollment |
| NCT05179876 | Phase 3 | Recruiting | 280 | Open-label long-term follow-up platform study for patients continuing selexipag/other PAH therapies after parent-trial closure; still accruing, no results yet |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30632656 | 2019 | RCT subgroup (GRIPHON post-hoc) | Eur J Heart Fail | Selexipag treatment outcomes in corrected CHD-PAH patients, a poor-prognosis subgroup analyzed from the pivotal randomized GRIPHON trial |
| 41429287 | 2025 | Phase 2 PK/Safety | Chest | Prospective multicenter Phase 2 study of selexipag PK, safety, tolerability and exploratory efficacy in children with PAH |
| 30545978 | 2019 | Review | Eur Respir J | Pediatric PAH update from the 6th World Symposium on Pulmonary Hypertension Task Force |
| 38276220 | 2023 | Review | J Pers Med | Current management and future directions for PAH associated with congenital heart disease |
| 33781364 | 2021 | Retrospective | Cardiol Young | Single-centre report on selexipag use in pediatric PAH, focused on CHD patients |
| 36204579 | 2022 | Cohort | Front Cardiovasc Med | Selexipag-based triple combination therapy improves prognosis in Chinese PAH patients |
| 33442633 | 2020 | Review/Real-world | Eur Heart J Case Rep | Contemporary use of selexipag in PAH-CHD: case series showing reduced disease progression and improved exercise capacity vs. parenteral prostacyclin risks |
| 29521655 | 2018 | Cohort/First report | Am J Ther | First report of selexipag use in CHD-associated PAH and Eisenmenger syndrome |
| 32394855 | 2020 | Case series | Kardiologiia | Real-world experience with selexipag in PAH, including corrected CHD patients from a national registry |
| 35000655 | 2022 | Case report | Cardiol Young | Transition from oral selexipag to subcutaneous treprostinil in a trisomy 21 patient with CHD-PAH |
Taiwan Market Information
Selexipag is currently not marketed in Taiwan (0 registered licenses). No TFDA product registrations are available for review at this time.
Safety Considerations
- Drug Interactions: 191 documented interactions (DDInter database). Notable moderate-severity interactions include:
- SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin) — risk of additive hypotension/volume depletion
- Sympathomimetics/vasopressors (epinephrine, ephedrine, phenylephrine) — selexipag’s vasodilatory effect may attenuate pressor response
- Other vasodilators (papaverine, phentolamine, diazoxide, amyl nitrite, glycerin, mannitol) — additive hypotensive risk
Package insert–level warnings and contraindications are currently unavailable (see data gaps below); the above DDI list should not be treated as exhaustive.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: CHD-PAH is a mechanistically well-justified extension of selexipag’s approved PAH indication, supported by a pivotal-trial subgroup analysis (GRIPHON), an ongoing Phase 3 long-term follow-up study, and multiple real-world case series/cohorts. However, the only indication-specific prospective interventional trial (Phase 4, NCT04435782) was terminated early due to severe under-enrollment (n=9), and Taiwan-specific regulatory and safety label data are missing — evidence supports advancement but not unconditional approval.
To proceed, the following is needed:
- TFDA package insert with warnings/contraindications (currently a blocking data gap)
- Detailed mechanism of action (MOA) documentation from DrugBank
- Taiwan market registration pathway, as the drug currently has 0 licenses / is not marketed locally
- Adequately powered prospective data in CHD-PAH specifically, given the terminated Phase 4 trial
Note on other candidates: This Evidence Pack contains 9 additional TxGNN-predicted indications for selexipag. Several — PAH associated with HIV infection, schistosomiasis, connective tissue disease, and chronic hemolytic anemia — share the same WHO Group 1 PAH mechanistic class and range from L2 (CTD-PAH, GRIPHON subgroup–supported) to L4 (research-question stage). Others — pulmonary arteriovenous malformation, hypotrichosis/alopecia-related conditions, and periodontal malformation syndrome — show no mechanistic or clinical support and are classified L5 (Hold); these likely reflect indirect knowledge-graph associations rather than genuine repurposing signals.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.