Fenofibrate
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Fenofibrate: From Hypertriglyceridemia to Homozygous Familial Hypercholesterolemia
One-Sentence Summary
Fenofibrate is a lipid-lowering drug originally used for hypertriglyceridemia and other forms of hyperlipidemia. The TxGNN model predicts it may be effective for homozygous familial hypercholesterolemia (HoFH). The supporting evidence is weak: the 1 clinical trial linked to this prediction tests a different drug (alirocumab), and the 10 publications are mostly general reviews and guidelines, plus one small 1984 study.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hypertriglyceridemia, hyperlipidemia, familial hyperlipidemia, familial combined hyperlipidemia, hypoalphalipoproteinemia (from the knowledge graph; the Singapore registration records contain no indication text) |
| Predicted New Indication | Homozygous familial hypercholesterolemia |
| TxGNN Prediction Score | 99.91% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 13 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Fenofibrate is a PPAR-alpha agonist. It mainly lowers triglycerides and raises HDL cholesterol, and it lowers LDL cholesterol only modestly. Detailed mechanism-of-action data were not available in the compiled data, so this description reflects its well-known pharmacology.
The model's prediction likely reflects the closeness of HoFH to fenofibrate's approved lipid disorders in the knowledge graph. Mechanistically, though, the link is weak. HoFH is driven by a defect in the LDL receptor pathway, which fenofibrate does not act on. A meaningful LDL-lowering effect is therefore unlikely.
The only human data point is a 1984 study in type II hyperlipoproteinemia. It reported that one HoFH patient showed the greatest fall in total and LDL cholesterol, which is anecdotal. At most, fenofibrate might serve as an adjunct for mixed lipid abnormalities, not as a primary LDL-lowering therapy for HoFH.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03510715 | Phase 3 | Completed | 18 | Open-label study of alirocumab (a PCSK9 inhibitor) on LDL-C in children and adolescents with HoFH. Fenofibrate is not studied, so it provides no direct evidence. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 6593751 | 1984 | Cohort | Pharmacol Res Commun | 22 patients with type II hyperlipoproteinemia given fenofibrate 300 mg/day. LDL-C fell about 24% overall and about 31% in familial hypercholesterolemia; one HoFH patient had the largest fall. |
| 28437620 | 2017 | Review | Endocr Pract | AACE/ACE guidelines on dyslipidemia management and cardiovascular prevention. General context only. |
| 37979722 | 2024 | Review | Indian Heart J | Non-statin lipid-lowering drugs. Fenofibrate's clearest indication is triglycerides >500 mg/dL, to reduce pancreatitis risk. |
| 2042836 | 1991 | Review | Ann N Y Acad Sci | Drug and surgical treatment of dyslipidemic children, mostly those with familial hypercholesterolemia. Fenofibrate is listed among agents that reduced lipids. |
| 35499807 | 2022 | Review | Curr Atheroscler Rep | Dyslipidemia management in pregnancy. Indirect relevance. |
| 14620392 | 2003 | Review | Pharmacotherapy | Ezetimibe as a cholesterol absorption inhibitor. Not about fenofibrate. |
| 9129869 | 1997 | Review | Drugs | Atorvastatin pharmacology and therapeutic potential. Not about fenofibrate. |
| 9627539 | 1998 | Review | Can J Cardiol | Advances in dyslipidemia drug treatment, focused on atorvastatin. |
| 26432726 | 2015 | Review | Indian Heart J | LDL cholesterol, statins and PCSK9 inhibitors. |
| 24734312 | 2014 | Pharmacokinetic study | Pharmacotherapy | Pharmacokinetic interactions of lomitapide (an HoFH drug) with several lipid-lowering agents, including fenofibrate. No efficacy data for fenofibrate in HoFH. |
Singapore Market Information
Thirteen valid single-ingredient registrations exist, with no cancelled licenses. Forms are oral capsules, tablets and film-coated tablets. The registration records contain no approved-indication text, so that column is omitted. The five main authorizations are listed below.
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| SIN13351P | Fenosup Lidose 160mg Capsule | Capsule |
| SIN13615P | Lipanthyl Penta Film Coated Tablet 145 mg | Tablet, film coated |
| SIN17013P | Tricor Tablet 160 mg | Tablet, film coated |
| SIN11612P | Lipanthyl Supra 160 Tablet 160 mg | Tablet, film coated |
| SIN16155P | EP-Feno Tablet 145 mg | Tablet |
Safety Considerations
- Contraindication-related conditions (knowledge graph, not label text): liver failure and liver disease, pancreatitis, gallbladder disease and gallstones (cholelithiasis), muscle disorders (myopathy, rhabdomyolysis), impaired renal function, and blood-cell disorders (thrombocytopenia, anemia, leukopenia, neutropenia, agranulocytosis).
- Drug Interactions: 100 interaction records were found. The examples reviewed were all of Moderate severity:
- Sulfonylureas (glimepiride, glipizide, glyburide, chlorpropamide, acetohexamide)
- Many insulin products
- Chenodeoxycholic acid
- Esomeprazole
For package-insert warnings and contraindications, please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: HoFH is caused by a defect in the LDL receptor pathway that fenofibrate does not act on. The only linked trial tests alirocumab, and the human data for fenofibrate amount to a single HoFH patient in a 1984 study. The TxGNN score is high, but no real evidence backs it.
To proceed, the following is needed:
- Direct clinical data on fenofibrate in HoFH, such as a small controlled study of LDL-C response on top of standard therapy (statins, PCSK9 inhibitors, lomitapide)
- A clear clinical role defined (adjunct for mixed lipid abnormalities versus LDL lowering), given that existing HoFH therapies act on the LDL pathway
- Package-insert warnings and contraindications from the Singapore registrations, for a safety review
- Review of the hepatic, renal, muscle and gallbladder risks and the interactions with antidiabetic drugs in the HoFH population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.