Selpercatinib
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Selpercatinib: From RET-Driven Cancers to Pulmonary Hypertension
One-Sentence Summary
Selpercatinib is a selective RET kinase inhibitor used in RET-driven cancers such as RET fusion-positive non-small-cell lung cancer and medullary thyroid carcinoma. The TxGNN model predicts it may be effective for pulmonary hypertension, but 0 clinical trials and 0 directly relevant publications support this direction. The three publications compiled concern cancer or safety, not pulmonary hypertension.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the approval records compiled for this report (the available literature points to RET-driven cancers) |
| Predicted New Indication | Pulmonary hypertension |
| TxGNN Prediction Score | 99.18% |
| Evidence Level | L5 |
| US Market Status | Cancelled only (both NDAs cancelled) |
| Number of NDAs | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, selpercatinib is a selective RET kinase inhibitor. Its use in RET-altered cancers is reflected in the literature compiled here (RET fusion NSCLC and RET-mutated medullary thyroid carcinoma).
The link to pulmonary hypertension is only indirect. Kinase signaling is involved in pulmonary vascular remodeling, and some other kinase inhibitors have been studied in pulmonary arterial hypertension. Conversely, some kinase inhibitors are associated with pulmonary vascular toxicity. No direct mechanistic or clinical evidence for RET inhibition in pulmonary hypertension is available.
The score is very high, but it comes from a graph-based computational prediction only. Two other predictions, migraine disorder (99.17%) and migraine with brainstem aura (99.05%), also have no trials or literature. The brainstem aura prediction is a subtype of the first, so it is not independent evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39372206 | 2024 | Real-world pharmacovigilance study | Front Pharmacol | Compares adverse event profiles of pralsetinib and selpercatinib using FDA adverse event reports. Relevant to safety context only |
| 34178121 | 2021 | Retrospective cohort | Ther Adv Med Oncol | Real-world use of selpercatinib in RET fusion-positive NSCLC through an access program |
| 41918669 | 2026 | Case report | Cureus | Long-term management and targeted therapy of metastatic medullary thyroid carcinoma in MEN 2B with RET M918T mutation |
None of these publications address pulmonary hypertension, so they do not support the predicted indication.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA218160 | RETEVMO | Tablet, coated | Not available (status: cancelled) |
| NDA213246 | RETEVMO | Capsule | Not available (status: cancelled) |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (selective kinase inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Drug Interactions: The interaction screening returned 100 interacting drugs in total. The first 20 listed include the following.
- Major: famotidine, ranitidine, cimetidine, rabeprazole, omeprazole, dexlansoprazole, aprepitant, dexamethasone, clarithromycin, magnesium oxide
- Moderate: hydrocortisone, triamcinolone, betamethasone, budesonide, pioglitazone, loperamide, saxagliptin, bisacodyl, polyethylene glycol (3350 with electrolytes)
Acid-reducing agents (H2 blockers, proton pump inhibitors, antacids) and strong CYP3A inhibitors or inducers (such as clarithromycin, aprepitant and dexamethasone) warrant particular attention.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a model score alone (Evidence Level L5). There are no clinical trials and no relevant literature, and the mechanistic link to pulmonary hypertension is speculative. Both US NDAs are cancelled, and package insert safety data are missing.
To proceed, the following is needed:
- Mechanism of action data, and a mechanistic rationale for RET inhibition in pulmonary vascular disease
- Preclinical studies in pulmonary hypertension models
- Package insert warnings and contraindications, in particular any pulmonary vascular or cardiovascular toxicity
- Clarification of the original approved indications and the reasons for the NDA cancellations
- A review of the drug interaction burden for the intended patient population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.