Gilteritinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Gilteritinib: From Acute Myeloid Leukemia to Bulbar Polio
One-Sentence Summary
Gilteritinib is an oral kinase inhibitor (FLT3/AXL) originally used to treat acute myeloid leukemia (AML). The TxGNN model predicts it may be effective for bulbar polio, with a very high score of 99.10%. However, there are 0 clinical trials and 0 publications supporting this prediction, so it is a model output only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Acute myeloid leukemia (from the knowledge-graph indication records; the Singapore registration record gives no indication text) |
| Predicted New Indication | Bulbar polio |
| TxGNN Prediction Score | 99.10% |
| 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. Based on known information, gilteritinib is a FLT3/AXL kinase inhibitor. Its efficacy in FLT3-mutated AML is the basis of its use, but there is no evident mechanistic link to bulbar polio.
Bulbar polio is a viral infection in which poliovirus attacks motor neurons in the brainstem. Nothing in the available data connects inhibition of FLT3 or AXL to poliovirus infection or to protection of motor neurons. The high score therefore looks like an artifact of the knowledge graph rather than a real biological signal. A high score with no supporting studies should not be read as evidence of efficacy.
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 |
|---|---|---|---|
| SIN16088P | XOSPATA® Film-Coated Tablets 40mg (Astellas Pharma Inc.) | Tablet, film coated (oral) | — |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (kinase inhibitor), not a conventional cytotoxic agent |
| 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 (at minimum, routine blood counts and liver and renal function are advisable for an anticancer agent) |
| Handling Protection | Please refer to the package insert and local institutional policy for handling of oral anticancer drugs |
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for these.
- Drug Interactions: 100 interacting drugs were identified; the 20 listed in the data include:
- Major: clarithromycin, dolasetron
- Moderate: famotidine, aprepitant, cimetidine, dexamethasone, palonosetron, levofloxacin, metformin, linagliptin, naltrexone, loperamide, miconazole, bisacodyl, picosulfuric acid, sodium sulfate, polyethylene glycol (3350 with electrolytes), eliglustat, metreleptin
- Minor: metronidazole
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on the model score alone. There are no trials or publications for bulbar polio, and no plausible mechanistic link to gilteritinib's targets. It is most likely a knowledge-graph artifact.
To proceed, the following is needed:
- A plausible biological rationale linking FLT3/AXL inhibition to poliovirus pathology, supported by preclinical data
- Mechanism of action data and package insert safety information (warnings, contraindications)
- Redirecting attention to better-supported candidates from the same prediction list:
- Myelodysplastic/myeloproliferative disease has early-phase evidence (L3). This includes a Phase 1/2 trial of azacitidine, venetoclax and gilteritinib in FLT3-mutated AML or high-risk MDS (NCT04140487), plus a case report of an FLT3-fusion neoplasm (PMID 33792628).
- Therapy-related AML/MDS (alkylating agent- or radiation-related) is biologically plausible but overlaps closely with the approved AML indications, so it is not a true repurposing candidate.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.