Eliglustat
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Eliglustat
- Eliglustat: From Gaucher Disease Type 1 to Polycystic Kidney Disease 3 (with or without Polycystic Liver Disease)
Eliglustat: From Gaucher Disease Type 1 to Polycystic Kidney Disease 3 (with or without Polycystic Liver Disease)
One-Sentence Summary
Eliglustat is a glucosylceramide synthase (UGCG) inhibitor originally approved for Gaucher disease type 1. Among 10 TxGNN-predicted indications in this evidence pack, Polycystic Kidney Disease 3 (with or without Polycystic Liver Disease) is the only one backed by real literature — 20 PubMed publications — but none of these papers study eliglustat itself, so the drug-disease link is currently a mechanistic hypothesis rather than demonstrated evidence. (The other 9 candidates, including the top-scoring “autosomal ichthyosis syndrome,” have zero clinical trials or literature and remain at Hold/S0.)
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Gaucher disease type 1 (from known drug class information — not confirmed via Taiwan/EU license text, as none exists; see EU Market Information below) |
| Predicted New Indication | Polycystic Kidney Disease 3 (with or without Polycystic Liver Disease) |
| TxGNN Prediction Score | 96.91% (model rank 24,423) |
| Evidence Level | L4 |
| EU Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Eliglustat is a glucosylceramide synthase (UGCG) inhibitor — a substrate reduction therapy originally approved for Gaucher disease type 1, a lysosomal storage disorder caused by glucocerebrosidase deficiency and glycosphingolipid accumulation.
The proposed link to polycystic kidney/liver disease is indirect: glycosphingolipid metabolism abnormalities have been discussed in some disease-mechanism literature on cystic epithelial proliferation and lipid signaling in PKD/PLD, which gives a theoretical, distal rationale for a UGCG-pathway drug to be of interest.
However, all 20 retrieved PubMed articles are general clinical guidelines, genetics reviews, and pathophysiology overviews of ADPKD/PLD — none of them mention eliglustat or UGCG inhibition specifically. They were captured because they match the disease term, not because they test the drug. This makes the prediction a research hypothesis worth exploring at the preclinical/mechanistic level, not evidence of a treatment effect.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29038287 | 2018 | Review | J Am Soc Nephrol | Genetic overlap and shared pathogenesis between ADPKD and ADPLD, including the genes underlying PKD3-type presentations |
| 38097330 | 2023 | Review | Adv Kidney Dis Health | Genetic spectrum of polycystic kidney/liver disease and resulting phenotypes; ciliary dysfunction central to pathogenesis |
| 30819518 | 2019 | Review | Lancet | Comprehensive ADPKD overview: cyst growth, hypertension, and extrarenal complications including liver cysts |
| 35487607 | 2022 | Review | Clin Liver Dis | Clinical course of PLD as the most common extrarenal manifestation of ADPKD |
| 40081770 | 2025 | Review | Biochem Pharmacol | Extracellular matrix and metalloprotease dynamics as therapeutic targets in PKD/PLD cyst progression |
| 34724412 | 2022 | Review | Annu Rev Pathol | Mechanistic sequence (primary/secondary/tertiary) of hepatic cystogenesis in PLD |
| 30652979 | 2019 | Review | Curr Opin Gastroenterol | Genetic mechanisms underlying polycystic liver disease |
| 35728731 | 2022 | Guideline | J Hepatol | EASL clinical practice guidelines on management of cystic liver diseases |
| 28317394 | 2017 | Review | Expert Rev Gastroenterol Hepatol | PLD as an inherited ciliopathy/cholangiopathy; epidemiology and natural history |
| 37943238 | 2023 | Review | Adv Kidney Dis Health | Extrarenal manifestations and complications of PLD in ADPKD patients |
EU Market Information
Eliglustat is currently not marketed in the EU (0 authorizations on file), so no product/dosage-form/indication data is available from the regulatory database.
Safety Considerations
Please refer to the SmPC for safety information. (No key warnings, contraindications, or DDI records are currently available for eliglustat in this evidence pack — TFDA label warnings/contraindications are flagged as a blocking data gap.)
Conclusion and Next Steps
Decision: Hold
Rationale: The only predicted indication with any literature support (PKD3/PLD) is backed exclusively by general disease-background reviews and guidelines, not by any study of eliglustat or UGCG inhibition — this is a research hypothesis, not clinical evidence. All other 9 predicted indications have zero clinical trials or literature (L5, Hold).
To proceed, the following is needed:
- TFDA/SmPC label data (warnings, contraindications) — currently a blocking data gap (DG001)
- Preclinical or mechanistic studies directly testing UGCG inhibition (eliglustat) in PKD/PLD models, since existing literature is disease-background only, not drug-specific
- If pursued, a formal literature/patent search restricted to “eliglustat” + “polycystic kidney/liver disease” or “UGCG” + “PKD” to confirm no prior art exists
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.