Selexipag
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Selexipag
- Selexipag: From Pulmonary Arterial Hypertension to PAH Associated with Congenital Heart Disease
Selexipag: From Pulmonary Arterial Hypertension to PAH Associated with Congenital Heart Disease
One-Sentence Summary
Selexipag is an oral selective prostacyclin (IP) receptor agonist, originally used to treat pulmonary arterial hypertension (PAH). The TxGNN model predicts it may be effective for pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), with no registered clinical trials but 15 publications, including a subgroup analysis of the randomised GRIPHON trial, currently supporting this direction. Because CHD-PAH is a subgroup of the already-approved PAH indication, this is better described as a population extension than a true repurposing.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Pulmonary arterial hypertension (the Singapore licence records contain no indication text, so this comes from the knowledge graph) |
| Predicted New Indication | Pulmonary arterial hypertension associated with congenital heart disease |
| TxGNN Prediction Score | 98.03% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 8 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. Selexipag is known as an oral selective IP prostacyclin receptor agonist. Its active metabolite causes pulmonary vasodilation and has antiproliferative effects on the pulmonary vasculature.
CHD-PAH belongs to Group 1 PAH, the same group as the already-approved indication. These vasodilatory and antiproliferative effects are therefore expected to apply regardless of PAH cause. Selexipag is also oral, which may avoid the risks of parenteral prostacyclin therapy that are a concern in CHD patients.
The supporting evidence is largely a GRIPHON subgroup analysis of patients with corrected CHD-PAH, plus case series and real-world reports (including Eisenmenger syndrome and paediatric patients). No dedicated trial exists for this subgroup.
Clinical Trial Evidence
Currently no related clinical trials registered for this indication.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 30632656 | 2019 | RCT subgroup analysis (GRIPHON) | Eur J Heart Fail | Characterises patients with CHD-PAH after defect correction and their response to selexipag; these patients have a poorer prognosis than other CHD-PAH patients |
| 41429287 | 2026 | Phase 2 single-arm study | Chest | Pharmacokinetics, safety and exploratory efficacy of selexipag in children with PAH |
| 29521655 | 2018 | Case series | Am J Ther | First report of selexipag in CHD-PAH and Eisenmenger syndrome |
| 38276220 | 2023 | Review | J Pers Med | Current management and future directions for CHD-PAH; novel agents have improved morbidity and mortality |
| 36286872 | 2021 | Review | Ter Arkh | Evidence base for PAH-specific vasodilators in adults with CHD; the only RCT is for bosentan, other drugs rely on uncontrolled trials |
| 33442633 | 2020 | Case series | Eur Heart J Case Rep | Oral selexipag may avoid the risks of parenteral prostacyclin in PAH-CHD |
| 33539988 | 2021 | Clinical report | Can J Cardiol | Use of selexipag in Eisenmenger syndrome, which was excluded from most PAH trials apart from bosentan |
| 33781364 | 2021 | Single-centre report | Cardiol Young | Experience with selexipag in four paediatric patients, focused on CHD |
| 41513133 | 2026 | Real-world observational | J Cardiol | Use of selexipag and parenteral prostacyclin analogs in Japan, by patient characteristics and PAH cause |
| 32394855 | 2020 | Clinical experience | Kardiologiia | Single-centre experience including 2 patients with corrected congenital heart defects |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15283P | UPTRAVI Film-Coated Tablet 200MCG | Film-coated tablet | Not stated in the licence data |
| SIN15284P | UPTRAVI Film-Coated Tablets 400MCG | Film-coated tablet | Not stated in the licence data |
| SIN15285P | UPTRAVI Film-Coated Tablets 600MCG | Film-coated tablet | Not stated in the licence data |
| SIN15286P | UPTRAVI Film-Coated Tablets 800MCG | Film-coated tablet | Not stated in the licence data |
| SIN15287P | UPTRAVI Film-Coated Tablets 1000MCG | Film-coated tablet | Not stated in the licence data |
All 8 registrations (200 to 1600 mcg) are valid single-ingredient oral products.
Safety Considerations
Drug Interactions: The interaction screen returned 100 interacting drugs. The 20 reviewed here were all rated Moderate. They include:
- SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin)
- Sympathomimetics and vasoactive agents (epinephrine, ephedrine, phenylephrine, phentolamine, papaverine, diazoxide)
- Nitrites (amyl nitrite)
- Others (mannitol, glycerin, amifostine, deferasirox, abiraterone, acebutolol)
For the full list, please refer to the package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: CHD-PAH is a subgroup of the approved PAH indication, and the GRIPHON subgroup analysis plus multiple case series and real-world reports support use. However, there is no dedicated trial in this population, so the evidence rests on subgroup and observational data.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (currently a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Approved indication text for the Singapore licences, to confirm whether CHD-PAH is already covered
- Dedicated or prospective data in CHD-PAH, including Eisenmenger syndrome and corrected versus uncorrected defects
- A review of drug interactions relevant to CHD-PAH patients
Other Predicted Indications (Brief Notes)
| Predicted Indication | Evidence Level | Decision | Note | |------|------|------|------| | PAH associated with connective tissue disease | L2 | Proceed with Guardrails | GRIPHON subgroup (n=334), a meta-analysis, and observational data; no dedicated trial | | PAH associated with schistosomiasis | L2 | Proceed with Guardrails | Phase 2 trial NCT04589390 (n=20, status unknown) and 2026 SELSCH publication (42111371); small study | | PAH associated with HIV infection | L4 | Research Question | Indirect evidence only; antiretroviral interactions need evaluation | | PAH associated with chronic hemolytic anemia | L4 | Research Question | Indirect evidence only; pathophysiology differs from Group 1 PAH | | Pulmonary arteriovenous malformation | L5 | Hold | No evidence; vasodilation could worsen shunting | | Hypotrichosis simplex of the scalp, congenital hypotrichosis milia, diffuse alopecia areata, malformation syndrome with odontal/periodontal component | L5 | Hold | Model prediction only, with no mechanistic basis |
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.