Aflibercept
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Aflibercept
- Pharmacist Assessment Report
- Aflibercept: From Metastatic Colorectal Cancer and Retinal Disease to Esotropia
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Aflibercept: From Metastatic Colorectal Cancer and Retinal Disease to Esotropia
One-Sentence Summary
Aflibercept is a VEGF trap originally used for metastatic colorectal cancer and for retinal diseases such as macular degeneration, retinal artery occlusion and diabetic macular oedema. The TxGNN model predicts it may be effective for esotropia, but this is a model prediction only, with 0 clinical trials and 0 publications supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic colorectal cancer, macular degeneration, retinal artery occlusion, diabetic macular oedema (the Australian licence record contains no indication text) |
| Predicted New Indication | Esotropia |
| TxGNN Prediction Score | 0.9938 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 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, aflibercept is a trap for VEGF-A, VEGF-B and placental growth factor (PlGF). Its efficacy in neovascular and oedematous retinal disease and in metastatic colorectal cancer is established, and it acts by blocking VEGF-driven angiogenesis and vascular leakage.
Esotropia is a strabismus disorder driven by oculomotor and binocular vision factors, not by VEGF-dependent neovascularisation. No direct mechanistic link between VEGF inhibition and esotropia has been established. The high score (0.9938) comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence, so it should be treated as a hypothesis only.
Clinical Trial Evidence
Currently no related clinical trials registered for esotropia.
Literature Evidence
Currently no related literature available.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 10505X | Eylea | Solution for intravitreal injection 4 mg in 100 microlitres (40 mg per mL) | Not listed in the data compiled for this report |
The only registered form is an intravitreal injection. Whether this route is suitable for esotropia has not been assessed.
Safety Considerations
- Drug Interactions: 78 potential interactions were identified. Major-level examples include deferiprone, samarium (153Sm) lexidronam, adalimumab, baricitinib, certolizumab pegol, cladribine and clozapine. Moderate-level examples include strontium chloride Sr-89, roflumilast, chloramphenicol, zidovudine, alefacept, alemtuzumab, anakinra, azathioprine and canakinumab. Only the first 20 entries were provided, so the list is incomplete. These interactions are most relevant to systemic exposure.
- Class concern: Anti-VEGF therapy carries a known risk of haemorrhage and gastrointestinal perforation when given systemically, which is relevant to the predicted varices indications.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction rests on a model score alone (L5). There are no supporting trials or publications, and no plausible mechanistic link between VEGF inhibition and esotropia. The only trial linked to any of the top-ranked predictions (NCT02537054, in pseudoxanthoma elasticum) concerns choroidal neovascularisation, an existing ocular use, and is not evidence for any predicted indication.
To proceed, the following is needed:
- Mechanism of action data and a mechanistic rationale for esotropia
- A systematic literature search and trial registry search (including ANZCTR) for aflibercept in strabismus
- The TGA Product Information, including warnings and contraindications, to complete safety screening
- Assessment of route and dosage form suitability for the proposed use
- Preclinical or early clinical data to move beyond L5
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.