Fedratinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Fedratinib: From Myelofibrosis to Benign PEComa
One-Sentence Summary
Fedratinib (brand name Inrebic) is an oral kinase inhibitor marketed in the US. It is generally known as a JAK2 inhibitor for myelofibrosis, though the supplied license data does not state the indication. The TxGNN model predicts it may be effective for benign PEComa, but there are 0 clinical trials and 0 publications supporting this direction, so it is a model prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Myelofibrosis (from general knowledge; the supplied license data lists no approved indication text) |
| Predicted New Indication | Benign PEComa |
| TxGNN Prediction Score | 99.84% |
| Evidence Level | L5 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the supplied data. Fedratinib is a kinase inhibitor, and the evidence pack refers to JAK2/FLT3 inhibition as its known targets.
The link to the predicted disease is weak. PEComa biology centers on mTOR pathway activation (TSC1/TSC2 loss), and no direct connection to JAK2/FLT3 inhibition is established in the supplied data. The high score (99.84%) most likely reflects similarity in the knowledge graph rather than a validated mechanism. Any mechanistic link would be speculative.
The top-ranked predictions show the same pattern:
- PEComa-family and mTOR-driven diseases (lymphangiomyoma, uterine PEComa, lymphangioleiomyomatosis): mTOR inhibitors are the established approach, and nothing supplied links fedratinib to this pathway.
- Rhabdoid tumor, familial rhabdoid tumor and dermatofibrosarcoma protuberans: these are driven by SMARCB1 loss or PDGFR signaling, with no documented link to the drug’s targets.
- Hemophagocytic lymphohistiocytosis (HLH) (infection-associated and malignancy-associated): these have the most plausible rationale, because JAK-STAT-driven cytokine storm makes JAK inhibition a reasonable hypothesis. They are labeled “Research Question”, but still have no fedratinib-specific evidence. Their identical scores suggest a shared graph neighborhood rather than independent support.
- Familial Mediterranean fever: a JAK-inhibitor rationale via cytokine signaling is conceivable but unsupported.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| NDA212327 | Inrebic (Celgene Corporation) | Capsule (oral) | Not listed in the supplied data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (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
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is model-only (L5) with no clinical trials or literature. The mechanistic link between JAK2/FLT3 inhibition and mTOR-driven PEComa is speculative. Safety data and mechanism of action are also missing, which blocks safety screening.
To proceed, the following is needed:
- The FDA package insert (warnings and contraindications), to allow safety screening
- Detailed mechanism of action data (for example from DrugBank)
- Preclinical or mechanistic evidence connecting fedratinib to PEComa biology, or a decision to prioritize the HLH-related predictions, which have a more plausible JAK-STAT rationale
- A literature and trial search for class-level JAK inhibitor evidence, with evidence graded separately from fedratinib-specific data
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.