Fedratinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Fedratinib: From Myelofibrosis to Benign PEComa
One-Sentence Summary
Fedratinib is an oral kinase inhibitor originally used to treat primary myelofibrosis and myelofibrosis. The TxGNN model predicts it may be effective for benign PEComa, but currently there are 0 clinical trials and 0 publications supporting this prediction, so it rests on model output alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Primary myelofibrosis / myelofibrosis (the approved indication text in the Singapore licence record is empty, so this comes from the knowledge-graph indication data) |
| Predicted New Indication | Benign PEComa |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| 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 known information, fedratinib is a JAK2/FLT3 inhibitor. Its efficacy in myelofibrosis, a disease driven by dysregulated JAK/STAT signalling, has been established.
PEComa (perivascular epithelioid cell tumour) is typically driven by mTOR pathway activation through TSC1/TSC2 loss. A link between this biology and JAK/STAT signalling is speculative and not supported by the data compiled. The prediction most likely reflects patterns in the knowledge graph rather than a demonstrated pharmacological connection.
Other top-ranked predictions fall into several groups:
- mTOR/TSC-driven diseases: lymphangiomyoma, uterine corpus PEComa, lymphangioleiomyomatosis
- Sarcomas and rhabdoid tumours: dermatofibrosarcoma protuberans, rhabdoid tumour, familial rhabdoid tumour
- Inflammatory and cytokine-driven diseases: familial Mediterranean fever, and two forms of haemophagocytic lymphohistiocytosis (HLH)
For HLH, JAK inhibition has a class-level biological rationale (for example with ruxolitinib), but no fedratinib-specific data are available. All of these predictions have an evidence level of L5.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16617P | INREBIC CAPSULES 100 MG (Celgene International Sarl) | Capsule | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (JAK2/FLT3 kinase inhibitor), not a conventional cytotoxic agent |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (anaemia, thrombocytopenia and neutropenia are known concerns for this class) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC (with differential), liver and renal function; other items per the package insert |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report, so please refer to the package insert for safety information. Fedratinib carries a known Wernicke's encephalopathy warning, and its myelosuppression is a concern in critically ill patients.
Drug Interactions: The interaction query found 100 potential interactions. The main ones listed here are:
- Major: dexamethasone, clarithromycin, eliglustat, naloxegol
- Moderate: proton pump inhibitors (rabeprazole, omeprazole, lansoprazole), other corticosteroids (hydrocortisone, triamcinolone, betamethasone, budesonide), aprepitant, cimetidine, saxagliptin, naldemedine, naltrexone
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported by model output only (L5), with no clinical trials or publications. The proposed mechanistic link between JAK2/FLT3 inhibition and mTOR-driven PEComa biology is speculative. Safety data from the package insert are also missing.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website
- Detailed mechanism of action data (MOA) from DrugBank
- Preclinical or mechanistic evidence linking JAK/STAT or FLT3 signalling to PEComa
- A literature and trial search for fedratinib in PEComa and in the other predicted diseases (for example HLH)
- A review of the major drug interactions, particularly with CYP3A4-related agents
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.