Parmodia (pemafibrate) / Kowa - LARVOL DELTA

A Phase III Confirmatory Study of K-877 (Pemafibrate) in Patients With Hypercholesterolemia and Statin Intolerance (clinicaltrials.gov) - P3 | N=71 | Completed | Sponsor: Kowa Company, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders

Disproportionality analysis of biliary adverse events associated with fibrates using the JADER and FAERS databases. (PubMed, Front Pharmacol) - "A significant signal for biliary ADEs was detected for fibrates in both databases, with a particularly consistent association for pemafibrate. Regular hepatobiliary monitoring and individualized patient management are recommended."

Adverse events • Journal

Ketogenic Nutrition in Combination With PPARα Activation Induced Metabolic Failure and Exacerbated Muscle Weakness in Septic Mice. (PubMed, J Cachexia Sarcopenia Muscle) - "In septic mice, pemafibrate combined with balanced-TPN or lipid-rich TPN induced PPARα activation but did not result in ketosis nor affect muscle weakness. Pemafibrate combined with pure LCTs induced ketosis in sepsis but worsened muscle weakness, possibly explained by muscular bioenergetic failure."

Journal • Preclinical • Infectious Disease • Septic Shock • ACOX1 • CD36 • CPT1A • HMGCS2 • PPARA • SCARB1

Impact of PNPLA3 Genotype on Hepatic Steatosis Response to Pemafibrate in MASLD With Dyslipidemia. (PubMed, Hepatol Res) - "Pemafibrate reduced hepatic steatosis preferentially in PNPLA3 CC carriers, whereas PNPLA3 G-allele carriers showed attenuated CAP improvement without weight loss. PNPLA3 polymorphism may influence steatosis-lowering efficacy of pemafibrate, underscoring the need for genotype-informed therapeutic strategies."

Journal • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PNPLA3

Effects of pemafibrate (a selective PPAR-α agonist) versus weight loss through an intensive lifestyle modification on liver enzymes, serum soluble dipeptidyl peptidase-4, and hepatic steatosis and fibrosis evaluated by FibroScan transient elastography in people with type 2 diabetes and MASLD. (PubMed, Clinics (Sao Paulo)) - "In people with type 2 diabetes and MASLD, although weight loss through an ILI was better than pemafibrate in terms of the main indicators that assess improvements in the pathogenesis of MASLD, such as CAP, pemafibrate is as effective as moderate weight loss for decreasing liver enzymes or serum sDPP-4/CD26."

Journal • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • DPP4

The role of the PPAR system in diabetic cardiovascular risk and beyond. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "These diversified effects, albeit with a limited risk of significant side effects, make PPAR agonists an area of growing interest and with an expanding range of potential applications."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Peripheral Arterial Disease • Type 2 Diabetes Mellitus

Selective Peroxisome Proliferator-Activated Receptor-α (PPARα) Modulator Inhibits Cyst Enlargement in PKD (KIDNEY WEEK 2025) - "Although fenofibrate, a PPARα modulator, has been reported to suppress renal cyst enlargement, it has not yet been applied clinically due to concerns about renal metabolism and nephrotoxicity. Conclusion The favorable effects of pemafibrate in animal models of cystic kidney disease and cellular experiments demonstrated its potential as a clinical treatment for ADPKD. We will evaluate the optimal dosage and toxicity of pemafibrate treatment."

Autosomal Dominant Polycystic Kidney Disease • Fibrosis • Genetic Disorders • Immunology • Nephrology • Polycystic Kidney Disease • Renal Disease • PPARA

Peroxisome Proliferator-Activated Receptor α Modulator Pemafibrate Ameliorates Salt-Sensitive Hypertension and Hypertensive Organ Damage After Ischemia-Reperfusion Injury in Rats (KIDNEY WEEK 2025) - "Conclusion Pemafibrate, a selective PPARα modulator, ameliorates salt-sensitive hypertension and hypertensive kidney injury after IRI in rats by suppressing NLRP3-mediated inflammation and inhibiting NCC activation. These findings suggest pemafibrate as a potential therapeutic agent for salt-sensitive hypertension and its associated organ damage."

Preclinical • Cardiovascular • Fibrosis • Hypertension • Immunology • Inflammation • Renal Disease • Reperfusion Injury • CASP1 • CD68 • IL1B • NLRP3 • PPARA

Renoprotective Effects of Pemafibrate in Patients with CKD: An Open-Label, Randomized, Controlled Trial (PROFIT-CKD Study) (KIDNEY WEEK 2025) - "Notably, this effect was similarly observed in the obese (BMI ≥ 25 kg/m 2 ) subgroup of patients with diabetic nephropathy (least squares mean difference: 7.2; P = 0.02), but not in the group without obesity (least squares mean difference: 0.15; P = 0.95). Conclusion In non-dialysis CKD patients, Pemafibrate treatment did not significantly alter proteinuria compared to conventional therapy; however, it may be beneficial in patients with diabetes nephropathy, especially with obesity."

Clinical • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Nephrology • Obesity • Renal Disease • PPARA

Bezafibrate, a Pan PPAR agonist, attenuates experimental rheumatoid arthritis via PPAR dependent modulation of inflammatory pathways with emphasis on PPAR γ activity. (PubMed, Int Immunopharmacol) - "Initially, molecular docking was performed using a panel of fibrate-class compounds (including pemafibrate, bezafibrate, fenofibrate, gemfibrozil, and clofibrate) against the ligand-binding domain of PPAR-γ (PDB ID: 7WGO). These findings suggest that bezafibrate, selected through integrative computational and pharmacological screening, effectively ameliorates experimental autoimmune arthritis via PPAR-γ activation. This highlights its promise as a repurposed therapeutic candidate and warrants further investigation."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL1B • IL6 • TNFA

Triglyceride Lowering with Pemafibrate to Reduce Fibrinogen - PEMA-TAS study - (AHA 2025) - "Pemafibrate significantly reduced fibrinogen levels in patients with CAD and hypertriglyceridemia, highlighting its primary benefit in lowering thrombotic risk. While increases in AR-AUC and PL-AUC were observed as secondary outcomes, their implications require further investigation to fully understand potential effects on thrombogenicity."

Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia • Thrombosis

Role of Ketone Body Metabolism in MASLD Progression and Pemafibrate Efficacy (AHA 2025) - "Moreover, the beneficial effects of PEMA on fatty liver appear to require intact ketone metabolism, suggesting that individual differences in therapeutic response may be influenced by metabolic status. These findings highlight the potential of ketone body metabolism as a novel therapeutic target for MASLD."

Clinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cancer • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Solid Tumor • ALDH2 • HMGCS2 • SDHA

Not all fibrates are made equal: Learning from biology and clinical trials. (PubMed, Atherosclerosis) - "However, only fenofibrate appears to reduce apoB, whereas gemfibrozil and pemafibrate do not. Real-world efficacy studies and CVD outcome trials have shown that fenofibrate may be an option in combination with statins compared to other fibrates and is well tolerated. Additionally, evidence from real-world studies of the fenofibrate-statin combination in patients over a period of up to 20 years has dispelled safety concerns regarding long-term use of fenofibrate."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • APOB

Risk of Venous Thromboembolism with Pemafibrate in Dyslipidemia: A Nationwide, Retrospective, Cohort Study Using a Japanese Claims Database. (PubMed, Ther Innov Regul Sci) - "We found no increase in VTE risk associated with pemafibrate in clinical practice in Japan."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • Venous Thromboembolism

EFFECTS OF COMBINATION THERAPY WITH PEMAFIBRATE AND SODIUM GLUCOSE COTRANSPORTER-2 INHIBITOR ON METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE WITH HYPERTRIGLYCERIDEMIA AND TYPE 2 DIABETES MELLITUS (UEGW 2025) - "Combination therapy with pemafibrate and an SGLT2 inhibitor improved liver function in patients with MASLD, HTG and T2DM compared to monotherapy. These findings suggest that combination therapy may offer synergistic benefits in managing the complex pathophysiology of MASLD."

Combination therapy • Diabetes • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • PPARA

THE CLINICAL EFFICACY OF A PPARΑ AGONIST ON MURINE PRIMARY BILIARY CHOLANGITIS (AASLD 2025) - "Background: Peroxisome Proliferator-Activated Receptor (PPAR) agonists, such as bezafibrate, elafibranor, and seladelpar, are recognized as one of the second-line treatments for primary biliary cholangitis (PBC)...Mice were fed either a normal/control diet (n=8) or a diet containing low (0.01 mg/100 g, n=6) or high (0.03 mg/100 g, n=6) doses of pemafibrate (PEM), a selective PPARα modulator, for 8 weeks... Our findings suggest that PPARα agonist exerts anti-inflammatory and anti-fibrotic effects in PBC through FXR suppression and improved BA composition. These effects collectively contribute to the amelioration of cholangitis and hepatic fibrosis in this PBC murine model. These findings support PPARα agonists as a rational adjunct therapy for PBC."

Preclinical • Cholestasis • Fibrosis • Hepatology • Immunology • Inflammation • Primary Biliary Cholangitis • COL1A1 • CX3CL1 • IL1B • IL6 • MMP2 • NFKBIA • NLRP3 • PPARA

EFFECTS OF PEMAFIBRATE ON IMPROVEMENT AND RECURRENCE IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE (MASLD) (AASLD 2025) - "PEM therapy led to normalization of ALT levels in approximately half of MASLD patients with dyslipidemia. However, about 20% experienced recurrence, highlighting the importance of sustained lifestyle modification alongside pharmacotherapy."

Clinical • Diabetes • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Pemafibrate Increases Circulating Angiopoietin-like Proteins 3 and 4 Without Promoting Pro-Atherogenic Changes in LDL and HDL Subspecies: A Post-Hoc Analysis of the PRESTIGE Study. (PubMed, J Atheroscler Thromb) - "Pemafibrate markedly elevated circulating ANGPTL3 and ANGPTL4 levels, but these increases were not associated with pro-atherogenic changes in lipoprotein profiles. Notably, baseline ANGPTL3 concentrations may influence the effect of fibrates on LDL-C levels."

Journal • Retrospective data • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ANGPTL3 • ANGPTL8 • APOA1 • APOA2

Repositioning a drug for hyperlipidemia as a potential senotherapeutic for aging-related respiratory diseases (ERS 2025) - "To evaluate the antifibrotic effects of pemafibrate, we compared the jet nebulizer method with a drug- mixed diet in bleomycin (BLM)-induced lung fibrosis mouse models. Nebulized administration of pemafibrate may be a promising therapeutic option for aging-related lung diseases. Focusing on drug repositioning, we are currently developing strategies to prolong the retention of pemafibrate in the lungs."

Chronic Obstructive Pulmonary Disease • Diabetes • Dyslipidemia • Fibrosis • Immunology • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • PPARA

Calculated Excess-Triglyceride Based on the Friedewald Formula is a Possible Surrogate Marker for the Production of Large Very-Low Density Lipoprotein, A Post-Hoc Analysis of the PROUD48 Study. (PubMed, J Atheroscler Thromb) - "The behavior of Ex-TG appears consistent with previous kinetic studies showing that omega-3FAs primarily suppress VLDL1 production, whereas fibrates promote TG removal, suggesting that Ex-TG serves as a surrogate marker for VLDL1 overproduction."

Journal • Retrospective data • Dyslipidemia • Metabolic Disorders • APOB

Effect of Pemafibrate on Metabolic Dysfunction-Associated Steatotic Liver Disease: A Nationwide Multicenter Study. (PubMed, JGH Open) - "Pemafibrate treatment significantly improved ALT levels and ALT normalization rates in MASLD patients with hypertriglyceridemia, with improvement observed at three months and a sustained effect up to 12 months. This is a large-scale multicenter study to date evaluating pemafibrate in MASLD, providing robust evidence for its potential as a therapeutic option in this population."

Clinical • Journal • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Does Pemafibrate Lower Low-Density Lipoprotein-Cholesterol? (PubMed, J Atheroscler Thromb) - No abstract available

Journal • Dyslipidemia

The distinct effects of metformin and imeglimin on high glucose-induced alterations in metabolic function and reactive oxygen species production in mouse Schwann cells are modulated by pemafibrate and/or fatty acid-binding proteins. (PubMed, Front Cell Neurosci) - "Imeglimin exerted beneficial biological effects by enhancing the energetic state and reducing ROS production without inducing metabolic quiescence in high glucose-treated SCs. These findings suggest that Ime has therapeutic potential for DPN, although its effects may be modulated by intracellular lipid metabolism."

Journal • Preclinical • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Pain • FABP5 • FABP7 • PPARA

Pemafibrate treatment produces antidepressant-like effects in CUMS and CRS models through activation of hippocampal PPARa and BDNF signaling. (PubMed, Int J Neuropsychopharmacol) - "Pemafibrate exerts antidepressant-like effects in both CUMS and CRS mouse models by promoting hippocampal PPARα and BDNF signaling."

Journal • CNS Disorders • Depression • Psychiatry • PPARA

Effect of pemafibrate on high-density lipoprotein cholesterol levels and subspecies in a patient with cholesteryl ester transfer protein deficiency: A case report with mechanistic insights. (PubMed, J Clin Lipidol) - "Herein, we describe the unexpected finding of a marked reduction in HDL-C levels in a patient with CETP deficiency following pemafibrate treatment. To better understand this paradoxical response, we analyzed the patient's clinical data and investigated potential mechanisms underlying pemafibrate's effects on HDL metabolism."

Journal • Cardiovascular • Dyslipidemia • Genetic Disorders • Metabolic Disorders • APOE