Avapritinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Avapritinib: From KIT/PDGFRA Inhibition to Axial Spondylometaphyseal Dysplasia
One-Sentence Summary
Avapritinib is an oral KIT/PDGFRA kinase inhibitor marketed in the US as Ayvakit. The approved indication text is not included in the supplied data. The TxGNN model predicts it may be effective for axial spondylometaphyseal dysplasia, a rare skeletal dysplasia. There are 0 clinical trials and 0 publications supporting this direction, so the prediction rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not listed in the supplied data |
| Predicted New Indication | Axial spondylometaphyseal dysplasia |
| TxGNN Prediction Score | 99.92% |
| Evidence Level | L5 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 5 license records (all under NDA212608) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on known information, avapritinib is a KIT/PDGFRA kinase inhibitor. Its approved indication text was not supplied, so the link between its original use and the predicted one cannot be assessed.
No identifiable mechanistic link. Axial spondylometaphyseal dysplasia is a rare skeletal dysplasia, and KIT/PDGFRA inhibition has no known bearing on its pathogenesis. The 0.999 score is a model output only. It is not supported by biology, trials or literature.
Pattern across the top 10 predictions. Seven of the ten predicted diseases are ALS or related motor neuron disorders. These include ALS, its genetic-susceptibility and type 22 labels, late-adult lower motor neuron syndrome, monomelic amyotrophy and Mills syndrome. The rest are ultra-rare developmental or congenital syndromes, and none has a documented KIT/PDGFRA rationale. The only weak, indirect hypothesis is for ALS, where another tyrosine kinase inhibitor, masitinib, has been studied through KIT/CSF1R-mediated mast cell and microglia modulation. It is not established that avapritinib shares this effect or reaches the CNS at relevant exposure. The multiple ALS-related entries are likely one signal repeated, not independent evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
US Market Information
All five records are identical, so they are shown once.
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| NDA212608 | Ayvakit | Tablet, film coated (oral) | Blueprint Medicines Corporation |
Safety Considerations
- CNS risks flagged in the prediction rationale: labeled intracranial hemorrhage and cognitive effects. These are especially relevant because the predicted indications are neurological or developmental.
The package insert warnings and contraindications were not supplied. Please refer to the package insert for full safety information. No drug interaction records were found.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is L5 (model score only), with no trials, no literature and no identifiable mechanistic link to a KIT/PDGFRA inhibitor. The labeled CNS risks add to the concern for neurological targets.
To proceed, the following is needed:
- The FDA package insert (warnings and contraindications). This blocks any safety screening.
- Mechanism of action data, to test whether any biological link exists.
- The approved indication text, to establish the original-to-new indication relationship.
- Any preclinical or clinical evidence for axial spondylometaphyseal dysplasia or, secondarily, for ALS. Without it, this candidate should not advance.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.