fenofibric acid / Generic mfg. - LARVOL DELTA

Assessing the real-world safety of fenofibric acid for hyperlipidemia: results from WHO-VigiAccess and FAERS databases. (PubMed, Front Med (Lausanne)) - "In addition to the known adverse reactions, this study has identified numerous potential adverse drug reactions associated with fenofibric acid. Although these findings require further validation through subsequent clinical trials, they provide valuable safety information for clinicians to consider when evaluating adverse effects in patients treated with fenofibric acid."

Journal • Real-world evidence • Allergy • Dyslipidemia • Fatigue • Gout • Hypertriglyceridemia • Hypoglycemia • Inflammatory Arthritis • Metabolic Disorders • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Pancreatitis • Renal Disease • Rheumatology • PPARA

Nanoparticles-mediated mitochondrial relocation of lipid-lowering drugs shape energy metabolism to conquer acquired immune resistance. (PubMed, Drug Resist Updat) - "Then, it was also revealed that clinical usable lipid-lowering drugs with mitochondria oxidative phosphorylation (OXPHOS) and glycolysis inhibiting capacity, like fenofibric acid (FFA), exhibited desired programmed death ligand-1 (PD-L1) and CD276 co-suppression capacity...Moreover, the combination therapy of IR-FFA@Alb nanoparticles and radiotherapy (RT) effectively avoid the frequently occurred immune tolerance phenomenon of RT by co-depression CD276 and PD-L1. These results altogether showed the possibility of using lipid-lowering drugs as multi-functional immune checkpoint inhibitors to sensitize tumor therapy."

IO biomarker • Journal • CNS Disorders • Depression • Oncology • Psychiatry • CD276 • PD-L1

Antiepileptic drugs and lipid-lowering agents in surface water in Colombia: occurrence, ecological threat, and removal strategies. (PubMed, Environ Sci Pollut Res Int) - "The findings revealed the presence of antiepileptic drugs such as carbamazepine (CBZ), 10,11-dihydro-10,11-dihydroxycarbamazepine (CBZ-Diol), and gabapentin (GBP). Detected lipid-lowering agents included fenofibric acid (FFA) and gemfibrozil (GFZ)...Findings underscore the need for pharmaceutical monitoring and management in water sources. Removing these compounds remains challenging due to their variable removal patterns, necessitating the development of effective mitigation strategies."

Journal

Design, synthesis, and evaluation of small molecule modalities for diabetic retinopathy (ACS-Fall 2025) - "Fenofibric acid, the active metabolite of fenofibrate and a known peroxisome proliferator-activated receptor alpha (PPARa) agonist, significantly reduces DR progression, as demonstrated in two independent clinical trials (FIELD and ACCORD). 3) Dual PPARα/RXRα agonism: due to the permissive nature of this heterodimeric pairing, we are pursuing dual agonists, which are expected to enhance potency and therapeutic outcomes. Progress in all three areas will be presented."

Diabetes • Diabetic Retinopathy • Metabolic Disorders • Retinal Disorders • PPARA • STING

Next generation approaches to small molecule PPARα agonism for retinal diseases (ACS-Fall 2025) - "PPARα has been clinically validated as a viable target for DR, as Fenofibrate (Feno), a clinically approved drug for hyperlipidemia, exhibited robust protective effects against disease progression and retinal neovascularization (NV) in type 2 diabetic patients. The protective effects of Feno on retinal inflammation, neuroprotection, NV and DR are unrelated to its lipid-lowering activity but rather result from agonism of PPARα by its major metabolite, fenofibric acid (FA)...In part I, the development of orally bioavailable NFPαAs will be discussed along with new data on formulations that provide >6-months of efficacy after a single intravitreal injection in animal models. In part II, data from a new initiative aimed at leveraging polypharmacology will be reported with the story of BH400, a dual PPARα (agonist) and STING (inhibitor) modulator."

Age-related Macular Degeneration • Diabetes • Diabetic Retinopathy • Dyslipidemia • Inflammation • Metabolic Disorders • Ocular Inflammation • Ophthalmology • Retinal Disorders • Type 2 Diabetes Mellitus • PPARA • STING

PPAR-mediated reduction of lipid accumulation in hepatocytes involves the autophagy-lysosome-mitochondrion axis. (PubMed, Ann Med) - "HepG2 cells were treated with oleate/palmitate (O/P) to induce lipid accumulation and exposed to the PPARα agonist fenofibric acid, the γ agonist pioglitazone, the δ agonist seladelpar, or the dual α/γ agonist saroglitazar. All PPAR agonists were able to promote the clearance of lipids in cells loaded with long-chain fatty acids. The key role of acid hydrolysis to generate fatty acids, which can be then catabolized in the mitochondria, and the ability of the PPAR system to sustain each phase of this clearing process were elucidated."

Journal • PPARA • TFEB

Fenofibrate inhibits activation of cGAS-STING pathway by alleviating mitochondrial damage to attenuate inflammatory response in diabetic dry eye. (PubMed, Free Radic Biol Med) - "This study aims to investigate the role of the cGAS-STING signaling pathway in diabetic dry eye disease (DDE) and further explore the therapeutic efficacy and underlying mechanism of fenofibric acid in DDE. Further investigation revealed that fenofibrate alleviated corneal inflammation in diabetic mice by inhibiting reactive oxygen species (ROS) production, restoring mitochondrial membrane potential, and suppressing the activation of the cGAS-STING signaling pathway. In conclusion, this study highlights the crucial role of the cGAS-STING signaling pathway in DDE and proposes that fenofibrate alleviates mitochondrial damage to inhibit this pathway, offering novel strategy for the treatment of DDE."

Journal • Diabetes • Dry Eye Disease • Inflammation • Keratitis • Metabolic Disorders • Ocular Inflammation • Ophthalmology • CGAS • STING

Pharmacokinetics and Safety of Fenofibrate in Participants with Mild Hepatic Impairment or with Advanced Fibrosis due to Metabolic-Associated Fatty Liver Disease. (PubMed, J Clin Pharmacol) - "In the phase 2a study, participants with hypertriglyceridemia and advanced fibrosis due to MAFLD were randomly assigned (1:1) fenofibrate 48 mg (n = 15) or fenofibrate 145 mg (n = 16) combined with firsocostat 20 mg, taken orally once daily for 24 weeks. In the phase 2a study, three participants had grade 3 hypertriglyceridemia. Fenofibrate was well tolerated, and modest differences were observed in fenofibric acid exposure in participants with mild hepatic impairment or advanced fibrosis due to MAFLD."

Journal • PK/PD data • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Mitochondrial-Targeted Multifunctional Platinum-Based Nano "Terminal-Sensitive Projectile" for Enhanced Cancer Chemotherapy Efficacy. (PubMed, ACS Nano) - "Herein, a platinum-based terminal-sensitive projectile (TSB) which comprises a heterofunctional tetravalent platinum prodrug as the primary warhead, complemented by a guidance system incorporating triphenylphosphine (TPP) and a secondary warhead, FFa (Fenofibric acid) was developed...This design allows the TSB to be precisely targeted into intertumoral mitochondria as its targeting terminal, releasing free oxaliplatin (OXA) and FFa upon reaching its terminal destination...Furthermore, under near-infrared (NIR) irradiation, the IR780 component generates a phototherapeutic thermal effect and reactive oxygen species (ROS), which deplete intracellular glutathione (GSH) levels and facilitate Pt cross-linking with mtDNA. Both in vitro and in vivo studies have demonstrated that this comprehensive approach significantly enhances the sensitivity of tumor cells to platinum-based chemotherapeutic drugs."

Journal • Metabolic Disorders • Oncology

Significantly improving the solubility and anti-inflammatory activity of fenofibric acid with native and methyl-substituted beta-cyclodextrins via complexation. (PubMed, Sci Rep) - "The efficacy of FFA complexed with CDs in mitigating inflammation positions it as a promising new drug. Additionally, our findings reveal that incorporating FFA into the CD cavity as a drug release system enhances the pharmacological profile of this substance, FFA."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Pain • Rheumatology

AFRICA: Atorvastatin Plus Fenofibric Acid (TriLipix) in the Reduction of Intermediate Coronary Atherosclerosis (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: Piedmont Healthcare | N=18 ➔ 0 | Terminated ➔ Withdrawn

Enrollment change • Trial withdrawal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease

Administration time modify the anxiolytic and antidepressant effects of inulin via gut-brain axis. (PubMed, Int J Biol Macromol) - "Serum metabolomics analysis showed that the main differential metabolites, including fenofibric acid, 4'-Hydroxyfenoprofen glucuronide and 5-(4-Hydroxybenzyl)thiazolidine-2,4-dione may be vital for the anxiolytic and antidepressant effects of different inulin treatment times. Our results suggested that inulin administration in the evening was more effective in alleviating the inflammatory response and improving amino acids metabolism. This study provides a new potential link between the microbiota-gut-brain axis and chrono-nutrition, demonstrating that a more appropriate administration time results in a better intervention effect."

Journal • CNS Disorders • Depression • Inflammation • Mood Disorders • Psychiatry • Transplantation

MEMMAT: Antiangiogenic Therapy for Children with Recurrent Medulloblastoma, Ependymoma and ATRT (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Medical University of Vienna | Trial completion date: Apr 2026 ➔ Apr 2030 | Trial primary completion date: Apr 2026 ➔ Apr 2030

Trial completion date • Trial primary completion date • Brain Cancer • Ependymoma • Medulloblastoma • Oncology • Solid Tumor

A facile synthesis of 2-(4-((4-chlorophenyl)(hydroxy)methyl) phenoxy)-2-methylpropanoic acid: Metabolite of anti-hyperlipidemic drug Fenofibrate. (PubMed, Results Chem) - "The ketone group of fenofibric acid was reduced using sodium borohydride in one route whereas the hydrolysis of isopropyl ester of the reduced fenofibrate was achieved by the mild alkaline hydrolysis in the other path. Both the ways of synthesis furnished the desired compound in excellent yield and purity. The new synthetic congener was characterized by spectroscopic methods."

Journal

Fenofibric Acid has Distinct Molecular Location in Reconstituted Liver Membranes and Higher Affinity Compared to Pemafibrate (NLA 2024) - "Fenofibric acid had higher membrane affinity and more pronounced interactions in reconstituted liver membranes compared to pemafibrate. This may contribute to differences in pharmacologic properties and potential clinical outcomes."

Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • PPARA

Choline Fenofibrate and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia (clinicaltrials.gov) - P4 | N=56 | Recruiting | Sponsor: Seoul National University Bundang Hospital | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Mar 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Repositioning of the Antihyperlipidemic Drug Fenofibrate for the Management of Aeromonas Infections. (PubMed, Microorganisms) - "Its active metabolite, fenofibric acid, acts as an agonist to the peroxisome proliferator-activated receptor alpha (PPAR-α), a transcription factor involved in different metabolic pathways. This study provides evidence that fenofibrate offered some protection in vitro in macrophages against Aeromonas infection. However, further studies are needed with other bacteria to determine its potential antibacterial effect and the route by which this protection is achieved."

Journal • Infectious Disease • CCL3 • PPARA • TNFA

Different Coactivator Recruitment to Human PPARα/δ/γ Ligand-Binding Domains by Eight PPAR Agonists to Treat Nonalcoholic Fatty Liver Disease. (PubMed, Biomedicines) - "Using a time-resolved fluorescence resonance energy transfer assay, we analyzed the recruitment of four coactivator peptides (PGC1α, CBP, SRC1, and TRAP220) to human PPARα/δ/γ-ligand-binding domains (LBDs) using eight PPAR dual/pan agonists (bezafibrate, fenofibric acid, pemafibrate, pioglitazone, elafibranor, lanifibranor, saroglitazar, and seladelpar) that are/were anticipated to treat nonalcoholic fatty liver disease. Only five agonists (bezafibrate, pemafibrate, elafibranor, lanifibranor, and seladelpar) recruited all four coactivators to PPARδ-LBD, and their concentration-dependent responses differed from those of PPARα/γ-LBD. These results indicate that altered gene expression through consensus PPREs by different PPAR subtypes/agonists may be caused, in part, by different coactivators, which may be responsible for the unique pharmacological properties of these PPAR agonists."

Journal • Addiction (Opioid and Alcohol) • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • MED1 • PPARA

Fenofibrate Ameliorates Retinal Pigment Epithelium Injury Induced by Excessive Fat Through Upregulation of PI3K/AKT Signaling. (PubMed, Drug Des Devel Ther) - "The application of fenofibric acid resulted in the inhibition of NOX4, 3-NT, TNFα, ICAM1 and VEGF expression in ARPE-19 cells treated with PA. Meanwhile, in vivo dosing of fenofibrate ameliorated the downregulated amplitudes of ERG c-wave in HFD-fed mice and suppressed the HFD-induced oxidative injury and inflammatory response in RPE tissues. Our results suggested that fenofibrate ameliorated RPE cell damage induced by excessive fat in vitro and in vivo, in part, through activation of the PI3K/AKT signaling pathway."

Journal • Inflammation • Oncology • ICAM1 • NOX4 • TNFA

Overcoming Cancer Resistance to Platinum Drugs by Inhibiting Cholesterol Metabolism. (PubMed, Angew Chem Int Ed Engl) - "Platinum(IV) complexes FP and DFP with fenofibric acid as axial ligand(s) were designed to combat the drug resistance through regulating cholesterol metabolism besides damaging DNA. The reduction of cholesterol significantly relieved the drug resistance of cancer cells. The double-acting mechanism gave the complexes strong anticancer activity in vitro and vivo, particularly against cisplatin-resistant cancer cells."

Journal • Oncology • PPARA

Human carboxylesterase 1A plays a predominant role in hydrolysis of the anti-dyslipidemia agent fenofibrate in humans. (PubMed, Drug Metab Dispos) - "Significance Statement Fenofibrate can be completely converted to fenofibric acid in humans and subsequently exert its pharmacological effects, but the hydrolytic pathways of fenofibrate in humans have not been well investigated. This study reported that the liver was the predominant organ and human carboxylesterase 1A was the crucial enzyme involved in fenofibrate hydrolysis in humans."

Journal • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • PPARA

A Mendelian randomization study for drug repurposing reveals bezafibrate and fenofibric acid as potential osteoporosis treatments. (PubMed, Front Pharmacol) - " The present study provided evidence that BZF and FBA can increase BMD, suggesting their potential effects in preventing and treating OP. These findings potentially pave the way for future studies that may allow personalized selection of lipid-lowering drugs for those at risk of OP."

Journal • Dyslipidemia • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Safety and pharmacokinetic comparison between fenofibric acid 135 mg capsule and 110 mg enteric-coated tablet in healthy volunteers. (PubMed, Transl Clin Pharmacol) - "In addition, the enteric-coated tablet was smaller than the capsule, making it easier for patients to swallow. Clinical Research Information Service Identifier: KCT0007177, KCT0003304."

Journal • PK/PD data • Dyslipidemia • Metabolic Disorders

Patterns of Triglyceride Testing and Results Over Time among Patients with Diabetes and Severe Hypertriglyceridemia in US Clinical Practice (ENDO 2023) - "Study measures were assessed beginning with the first TG value and included: number of TG tests (all patients), days between tests (patients with =2 TG values), TG values by test (all patients), and TG values across tests (patients with =3 TG values receiving statins only or TG-targeting therapy only [fenofibrate, fenofibric acid, icosapent ethyl, gemibrozil, omega-3 fatty acid]). TG testing among patients with diabetes and SHTG is relatively infrequent in US clinical practice, and test results are highly variable. Understanding these patterns is important for identifying, testing, and treating patients with diabetes and SHTG to reduce health risks.*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins."

Clinical • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders

In Situ Vaccination with Mitochondria-Targeting Immunogenic Death Inducer Elicits CD8 T Cell-Dependent Antitumor Immunity to Boost Tumor Immunotherapy. (PubMed, Adv Sci (Weinh)) - "Herein, an immunogenic cell death (ICD) inducer for in situ vaccination, which is based on a mitochondria-targeting modification of fenofibric acid (FFa), a lipid-lowering drug with potential inhibitory efficacy of respiratory complex I is developed...In a poorly immunogenic 4T1 tumor model, a single intratumoral (i.t.) Mito-FFa injection turns immune-cold tumors into hot ones and elicits systemic tumor-specific CD8 T cells responses against primary and metastatic tumors. Furthermore, the synergistic effect with PD-L1 blockade and good bio-safety of i.t. Mito-FFa administration suggest the great translational potential of Mito-FFa in tumor immunotherapy."

Journal • Immune Modulation • Oncology • CALR • CD8 • STING