Midostaurin

證據等級: L5

預測適應症: 0 個

Midostaurin (DB06595): Drug Repurposing Assessment — TxGNN Prediction Data Unavailable

One-Sentence Summary

Midostaurin (Rydapt®) is a multi-targeted kinase inhibitor with established antineoplastic activity, notably approved in the EU for FLT3-mutated acute myeloid leukaemia and advanced systemic mastocytosis. The current Evidence Pack contains no TxGNN repurposing predictions for this compound, and two critical data fields — mechanism of action and national prescribing information — are missing. A complete drug repurposing evaluation cannot be conducted at this time; a Hold decision is recommended pending data remediation.

Quick Overview

Item	Content
Original Indication	FLT3-mutated AML; advanced systemic mastocytosis (sourced from general pharmaceutical knowledge — absent from Evidence Pack)
Predicted New Indication	Not available — TxGNN pipeline returned no candidates
TxGNN Prediction Score	Not available
Evidence Level	Not determinable
Denmark Market Status	Not found in Laegemiddelstyrelsen national registry
Number of Marketing Authorisations	0 (national registry query)
Recommended Decision	Hold

Why No Prediction Is Available

The Evidence Pack for midostaurin (DB06595) contains an empty predicted_indications array, meaning the TxGNN pipeline did not return any repurposing candidates as of the data cutoff (2026-04-04). Two upstream data gaps most likely caused this failure:

Missing mechanism of action (MOA). The DrugBank query returned a result record (query log ID 2, status: success), yet the original_moa field was not populated. Without a pharmacological mechanism profile, the TxGNN graph model lacks the node features needed to score drug–disease links reliably.

Missing regulatory prescribing information. The Laegemiddelstyrelsen registry query returned zero licences. Notably, midostaurin holds an EMA centralised marketing authorisation (Rydapt®, EU/1/17/1213, granted June 2017) for use in Denmark and other EU member states. The national registry query appears not to have captured this centralised pathway, leaving indication vocabulary unmapped. This directly limits disease-node alignment in the knowledge graph and may have suppressed candidate generation.

Until these gaps are resolved, any repurposing hypothesis for midostaurin would rest on the model’s structural graph inference alone, without pharmacological or regulatory context — which is insufficient for a clinical evaluation.

Denmark Market Information

The Evidence Pack reports zero marketing authorisations via the Laegemiddelstyrelsen national registry. Based on publicly available pharmaceutical records, Rydapt® (midostaurin 25 mg hard capsules, Novartis) holds an EMA centralised authorisation accessible in Denmark; however, this must be formally verified before the next pipeline run.

Note	Detail
National registry result	0 licences retrieved
Expected EMA authorisation	EU/1/17/1213 (Rydapt® — requires verification)
Recommended action	Query EMA EPAR database directly; confirm product is on the Danish formulary and retrieve the approved indication text for disease mapping

Cytotoxicity

Midostaurin is classified as an antineoplastic agent on the basis of its approved indications (AML, systemic mastocytosis) and its mechanism of action as a multi-targeted protein kinase inhibitor. The section below is based on general pharmaceutical knowledge, as the Evidence Pack did not supply drug-level safety data; all entries should be verified against the current SmPC before clinical use.

Item	Content
Cytotoxicity Classification	Targeted therapy — multi-targeted protein kinase inhibitor (FLT3, KIT, PDGFR, PKC isoforms, VEGFR-2)
Myelosuppression Risk	High when used in AML induction regimens (febrile neutropenia, anaemia, thrombocytopenia are well-characterised in combination with cytarabine/daunorubicin)
Emetogenicity Classification	Low to moderate
Monitoring Items	Full blood count with differential, liver function tests (ALT/AST/bilirubin), renal function, QTc interval, pulmonary function (interstitial lung disease risk)
Handling Protection	Must follow cytotoxic drug handling regulations per local pharmacy guidelines

Safety Considerations

The Evidence Pack did not contain safety warnings, contraindications, or drug interaction data for midostaurin. Please refer to the approved Summary of Product Characteristics (SmPC) for all safety information before any clinical or research use.

Conclusion and Next Steps

Decision: Hold

Rationale: The Evidence Pack is critically incomplete — no TxGNN repurposing predictions were generated, and the two data gaps classified as Blocking/High severity (prescribing information and MOA) directly prevent both the prediction pipeline from functioning and the safety screening from proceeding. Generating a repurposing recommendation under these conditions would not be clinically responsible.

To proceed, the following is needed:

Investigate empty prediction output — Determine whether the pipeline failed silently (e.g., DrugBank ID DB06595 not matched to a KG node, or all scores below the reporting threshold). Review run_kg_prediction.py logs for midostaurin.
Retrieve MOA data (DG002) — Query the DrugBank API for DB06595 pharmacology, mechanism of action, and drug categories. The query log confirms a successful DrugBank hit exists; the MOA field must be extracted and populated.
Retrieve national prescribing information (DG001) — Download and parse the Rydapt® SmPC from either the EMA EPAR database (EU/1/17/1213) or the Laegemiddelstyrelsen product portal to populate warnings, contraindications, and approved indication text.
Re-align disease vocabulary — Once the approved indication text is available, re-run disease mapping to ensure AML and mastocytosis nodes are correctly linked in the knowledge graph.
Re-generate Evidence Pack — After resolving all data gaps, re-execute the full evidence collection pipeline and regenerate this report. A complete evaluation with TxGNN predictions, clinical trial evidence, and safety screening should then be possible.

This report is intended for research purposes only and does not constitute medical advice. All repurposing candidates require clinical validation before any therapeutic application.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.