Parmodia (pemafibrate) / Kowa - LARVOL DELTA

The Effects of Pemafibrate on Fibrinogen and Thrombogenicity in Patients with Coronary Artery Disease. (PubMed, J Atheroscler Thromb) - "Pemafibrate significantly reduced fibrinogen levels in patients with CAD and hypertriglyceridemia, thus highlighting its primary benefit in lowering thrombotic risk."

Journal • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia • Thrombosis

PPARs in Diabetic Retinopathy: Pathophysiological Insights and Emerging Pharmacological Strategies. (PubMed, Can J Diabetes) - "PPARα agonists such as fenofibrate and pemafibrate exert antioxidant, anti-inflammatory, and vasoprotective effects, while PPARγ agonists (e.g., pioglitazone) improve insulin sensitivity and attenuate oxidative damage, albeit with safety concerns such as fluid retention. Dual PPARα/γ agonists, including saroglitazar, provide synergistic benefits by reducing leukostasis, neovascularization, and inflammatory signaling, whereas PPARβ/δ is gaining attention for its role in retinal energy metabolism...Targeting both PPAR and non-PPAR pathways may enable preventive and multimodal management of DR. Future efforts should prioritize early-stage interventions, combination strategies, and innovative ocular drug delivery systems to overcome current therapeutic limitations and shift from reactive to preventive care."

Journal • Review • Diabetes • Diabetic Retinopathy • Dyslipidemia • Inflammation • Metabolic Disorders • Preventive care • Retinal Disorders • AKR1B1 • PPARA

Pemafibrate Improves Lipid and Liver Metabolism in Adult GH Deficiency: A Prospective Observational Study. (PubMed, J Endocr Soc) - "Pemafibrate had beneficial effects on hypertriglyceridemia as well as liver metabolism of patients with AGHD. However, its efficacy was attenuated by obesity."

Journal • Observational data • Dyslipidemia • Endocrine Disorders • Genetic Disorders • Growth Hormone Deficiency • Growth Hormone Deficiency (Adult) • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

A multicenter, bidirectional cohort study on the use of pemafibrate in CKD dialysis patients with anemia (ChiCTR) - P=N/A | N=120 | Not yet recruiting | Sponsor: The First Affiliated Hospital of Xi'an Jiaotong University; The First Affiliated Hospital of Xi'an Jiaotong University

New trial • Anemia • Hematological Disorders

Metabolic dysfunction-associated steatotic liver disease (MASLD): definition, diagnosis, natural history, and treatment. (PubMed, Jpn J Radiol) - "Although no pharmacotherapies for MASLD are currently approved in Japan, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors have been reported to improve histological inflammation and fibrosis in patients with MASLD, and their approval for MASLD is anticipated. Similarly, statins and pemafibrate have shown improvements in liver function and steatosis in patients with dyslipidaemia and are already used in routine clinical practice for comorbid cases."

Journal • Review • Cardiovascular • Dyslipidemia • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Peroxisome Proliferator-Activated Receptor α/δ/γ Activation Profile by Endogenous Long-Chain Fatty Acids. (PubMed, Int J Mol Sci) - "FA ligands exhibited different coactivator preference compared to synthetic PPAR agonists, including approved drugs such as pemafibrate, seladelpar, and pioglitazone, suggesting that these agonists may regulate target gene transcription in a different manner than natural FA ligands. Such differences may be relevant to the pathogenesis of side effects of synthetic PPAR agonists occasionally observed in (pre)clinical studies."

Journal • MED1 • PPARA

Fibrates : Do They Still Have a Role in Therapy in 2025? (PubMed, Curr Atheroscler Rep) - "However, emerging evidence suggests that fibrates, particularly fenofibrate and pemafibrate, have beneficial effects on albuminuria, hepatic steatosis, and diabetic retinopathy, indicating pleiotropic metabolic benefits beyond lipid lowering. Fibrates remain therapeutically relevant in selected dyslipidaemic or metabolically altered phenotypes. Their future lies in precision metabolic therapy, targeting microvascular, hepatic, and renal complications within a personalised cardiometabolic approach."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Retinopathy • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Nephrology • Renal Disease • Retinal Disorders

Selective PPAR-α activation with pemafibrate attenuates macrophage-mediated progression of calcific aortic valve disease. (PubMed, bioRxiv) - "Pemafibrate slows experimental AS progression and valve calcification through modulation of macrophage-VIC crosstalk, independent of lipid lowering. These findings support further evaluation of pemafibrate as a potential pharmacological approach for CAVD and support further testing in randomized clinical trials."

Clinical • Journal • Cardiovascular • Inflammation • CD68 • GSPT1 • PPARA • RACK1

Sepsis and the Liver. (PubMed, Diseases) - "Future research should focus on developing representative models, validating biomarkers, and conducting clinical trials to enable personalized therapies that modulate inflammation, restore metabolism, and repair the gut-liver axis, with the goal of improving outcomes in SALI."

Journal • Review • Cholestasis • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Failure • Metabolic Disorders • Septic Shock • Transplantation • NLRP3 • PPARA

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