Lumacaftor
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Lumacaftor: From Cystic Fibrosis to Leprosy
One-Sentence Summary
Lumacaftor is a CFTR corrector, used in combination with ivacaftor, and was originally developed for the treatment of cystic fibrosis. The TxGNN model predicts it may be effective for leprosy, but there are currently no registered clinical trials and no publications supporting this prediction. It is a model-based prediction only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Cystic fibrosis |
| Predicted New Indication | Leprosy |
| TxGNN Prediction Score | 0.9944 |
| 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, lumacaftor is a CFTR corrector that is used with ivacaftor (a CFTR potentiator) and improves the folding and trafficking of defective CFTR protein. Its efficacy in cystic fibrosis is established.
No mechanistic link to leprosy is established from the data compiled. Leprosy is a chronic infection caused by Mycobacterium leprae, and CFTR correction has no established relevance to the pathogen or to disease pathogenesis. The very high TxGNN score (0.9944) reflects a TxGNN model (deep learning) prediction only. It may reflect indirect network associations, such as shared host-response or protein-folding pathways, but these are speculative and unverified.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11463H | Orkambi | Tablet containing lumacaftor 200 mg with ivacaftor 125 mg (oral) | Not available in the data compiled |
Safety Considerations
Drug Interactions: The interaction screen identified 226 potential interactions. Examples from the data compiled include:
- Major: eliglustat, naldemedine, naloxegol, rolapitant
- Moderate: proton pump inhibitors (omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, rabeprazole), ranitidine, corticosteroids (betamethasone, prednisone), antidiabetic agents (acetohexamide, glimepiride, linagliptin, pioglitazone, repaglinide), bupropion and nitisinone
Please refer to the TGA-approved Product Information (PI) for warnings, contraindications and other safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by the TxGNN model score, with no clinical trials, no publications and no established mechanistic link to leprosy. The evidence level is L5.
To proceed, the following is needed:
- Mechanism of action data (for example from DrugBank) to assess any plausible link to leprosy biology
- Preclinical or in vitro evidence of activity relevant to M. leprae infection or the host response in leprosy
- A literature and trial registry review (including ANZCTR) for any supporting studies
- Warnings and contraindications from the TGA-approved Product Information, which are needed for safety screening
- Review of the approved indication text for the ARTG entry
- Assessment of route compatibility and of the clinical interaction burden with drugs commonly used in leprosy treatment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.