Fenofibrate

Evidence Level: L5 Predicted Indications: 1

Table of Contents

  1. Fenofibrate
    1. Pharmacist Assessment Report
    2. Fenofibrate: From Hypertriglyceridaemia to Cholesterol-Ester Transfer Protein Deficiency
    3. One-Sentence Summary
    4. Quick Overview
    5. Why is This Prediction Reasonable?
    6. Clinical Trial Evidence
    7. Literature Evidence
    8. Australia Market Information
    9. Safety Considerations
    10. Conclusion and Next Steps
    11. Disclaimer

Pharmacist Assessment Report

Fenofibrate: From Hypertriglyceridaemia to Cholesterol-Ester Transfer Protein Deficiency

One-Sentence Summary

Fenofibrate is a lipid-lowering drug, recorded in the knowledge graph for hypertriglyceridaemia and several familial and combined hyperlipidaemias. The TxGNN model predicts it may be relevant to cholesterol-ester transfer protein (CETP) deficiency, but there are no registered clinical trials and only 3 preclinical or mechanistic publications, none of which studies the disease directly.

Quick Overview

Item Content
Original Indication Hypertriglyceridaemia, hyperlipidaemia, familial hyperlipidaemia, familial combined hyperlipidaemia, hypoalphalipoproteinaemia (relations recorded in the knowledge graph; the Australian licence record contains no approved indication text)
Predicted New Indication Cholesterol-ester transfer protein deficiency
TxGNN Prediction Score 0.9961
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?

Detailed mechanism of action data is not available in the data compiled for this report. From general pharmacology, fenofibrate is a PPAR-alpha agonist. It lowers triglycerides and tends to raise HDL cholesterol, through effects on lipoprotein lipase, apoA-I/apoA-II and apoC-III expression. This is background knowledge, not drawn from the compiled data.

The link to CETP deficiency is indirect and weak:

  • A 2010 mouse study combined a CETP inhibitor with a PPAR-alpha agonist (fenofibrate). It reported additive HDL-C increases and LDL-C reductions, but it did not involve a CETP-deficient population.
  • A 2001 mouse study linked fenofibrate-induced PLTP gene expression to HDL enlargement. This is a mechanism that may overlap with the HDL remodelling seen in CETP deficiency.
  • A 2018 study found that plasma HDL levels did not correlate with faecal cholesterol excretion or cholesterol efflux capacity. This undermines the assumption that raising HDL is a useful goal.

CETP deficiency already features markedly elevated HDL-C, so the case for giving an HDL-raising drug is weak, and the therapeutic target is unclear. The high TxGNN score is a model output and is not supported by clinical data.

Clinical Trial Evidence

Currently no related clinical trials registered.

Literature Evidence

PMID Year Type Journal Key Findings
20332533 2010 Preclinical (transgenic mice) J Cardiovasc Pharmacol Ther CETP inhibition (torcetrapib) plus PPAR-alpha agonism (fenofibrate) raised HDL-C and lowered LDL-C in human ApoB100/CETP transgenic mice
11342537 2001 Preclinical (mice) J Biol Chem Fenofibrate induced the PLTP gene, accounting for HDL enlargement in treated mice
30271349 2018 Preclinical/mechanistic Front Physiol Plasma HDL did not correlate with faecal cholesterol or cholesterol efflux capacity, so HDL function matters more than HDL-C level; not specific to fenofibrate in CETP deficiency

Australia Market Information

ARTG Number Product Name Dosage Form Approved Indication
ARTG 13469X FENOFIBRATE RBX Tablet 48 mg (oral) Not stated in the available record

This is a single-ingredient product with a valid licence. The list is complete.

Safety Considerations

Contraindication relations recorded in the knowledge graph (not label text) include:

  • Liver failure and liver disease
  • Pancreatitis
  • Gallbladder disease, cholelithiasis and cholecystolithiasis
  • Myopathy, muscular disease, rhabdomyolysis and familial periodic paralysis
  • Impaired renal function
  • Haematological conditions: thrombocytopenia, anaemia, leukopenia, agranulocytosis and neutropenia (including congenital forms)

Drug interactions: The interaction screen returned 100 records. The 20 shown are all rated Moderate, and the main groups are:

  • Sulfonylureas: acetohexamide, chlorpropamide, glimepiride, glipizide and glyburide
  • Many insulin products, including human, aspart, degludec, detemir, glargine, glulisine and lispro
  • Chenodeoxycholic acid
  • Esomeprazole

Please refer to the TGA-approved Product Information (PI) for authoritative warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: No clinical trial or publication directly studies fenofibrate in CETP deficiency, so the evidence level is L5. The available preclinical work is only indirect. Because CETP deficiency already raises HDL-C, the clinical rationale for fenofibrate is unclear despite the high model score.

To proceed, the following is needed:

  • A clear statement of the clinical benefit sought in CETP deficiency (the target is currently unclear)
  • Direct clinical or mechanistic studies in CETP-deficient patients
  • Mechanism of action data for fenofibrate
  • Approved indication text and safety sections from the TGA Product Information for ARTG 13469X
  • A safety review of the contraindication relations and interactions listed above

    Disclaimer

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

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