Parmodia (pemafibrate) / Kowa - LARVOL DELTA

Treatment with pemafibrate ameliorates fatty liver index and atherogenic lipid profiles in Japanese patients with type 2 diabetes mellitus. (PubMed, Front Endocrinol (Lausanne)) - "Pemafibrate ameliorates MASLD estimated by FLI in addition to various atherogenic lipid profiles in Japanese hypertriglyceridemia patients with T2DM in the past mean 5 years. An early intervention with pemafibrate might contribute to prevention of the development of MASLD and atherosclerotic cardiovascular disease."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus

Long-Term Safety and Efficacy of Pemafibrate to Treat Hyperlipidemia: Post-marketing Surveillance Over a 24-Month Observation Period in Japan. (PubMed, Adv Ther) - "This PMS study demonstrated the safety and efficacy of pemafibrate after long-term administration in patients with hyperlipidemia."

Journal • P4 data • Dyslipidemia • Hepatology • Metabolic Disorders • Musculoskeletal Diseases • Rheumatology

Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice. (PubMed, Antioxidants (Basel)) - "Compared to vehicle treatment, pemafibrate treatment significantly reduced the expression levels of hepatic NADPH oxidase subunit genes, M1 macrophages, inflammatory-cytokine-related genes and profibrotic genes in both WT and eNOSKO mice, along with reduction in hepatic oxidative stress assessed by dihydroethidium staining and 4-hydroxynonenal protein levels. Thus, pemafibrate ameliorated MASLD with reduction in oxidative stress and inflammation even in vascular endothelial dysfunction."

Journal • Preclinical • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • NOS3

Efficacy and safety of pemafibrate in patients with statin-intolerant hypercholesterolemia: results from a 12-week, randomized, double blind, placebo-controlled, phase 3 trial (ESC-WCC 2025) - No abstract available

Clinical • P3 data • Cardiovascular • Dyslipidemia

Telmisartan Reverses Hepatic Steatosis via PCK1 Upregulation: A Novel PPAR-independent Mechanism in Experimental Models of MASLD. (PubMed, Pharmacol Res) - "Targeting different intrahepatic pathways, both PPAR-dependent and independent, the combination of pemafibrate and telmisartan, each at half the individual dose, was equally effective as the full dose of either drug alone to reduce liver lipid accumulation in the rat model. Our findings support the repurposing potential of these drugs, with the additional advantage of addressing both hepatic and cardiometabolic MASLD-associated complications."

Journal • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PCK1 • PPARA

Histopathological changes in two patients with hypertriglyceridemia and metabolic dysfunction-associated steatotic liver disease treated with pemafibrate: a serial liver biopsy study. (PubMed, Clin J Gastroenterol) - "Pemafibrate may exert antifibrotic and anti-inflammatory effects in MASLD regardless of steatosis trends and that histological assessment remains crucial, especially when non-invasive markers provide inconsistent results. This is the first report to confirm histopathological improvement with pemafibrate via serial liver biopsy, offering important insights into its therapeutic potential for MASLD with dyslipidemia."

Journal • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

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) - No abstract available

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

Evaluation of the Short-term Effect of Pemafibrate on Liver Fibrosis Biomarkers Stratified by FIB-4 Index in Patients with Type 2 Diabetes Mellitus and Hypertriglyceridemia. (PubMed, Intern Med) - "ΔFIB-4 was inversely correlated with baseline FIB-4 and positively correlated with Δγ-glutamyl transpeptidase. Conclusions The short-term effect of PEMA on liver fibrosis markers was more pronounced in patients with T2DM and hypertriglyceridemia who exhibited elevated baseline FIB-4 values."

Biomarker • Journal • Diabetes • Dyslipidemia • Fibrosis • Hypertriglyceridemia • Immunology • Liver Cirrhosis • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and safety of pemafibrate administration in patients with dyslipidemia: a systematic review and updated meta-analysis of randomized controlled trials. (PubMed, Ann Med Surg (Lond)) - "Pemafibrate improved the overall lipid biomarkers compared to placebo groups, demonstrating a significant reduction in triglycerides, non-HDL-C, and total cholesterol while increasing HDL-C. Moreover, there was no significant difference in adverse effects."

Journal • Retrospective data • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

Biochemical and Plasma Lipid Responses to Pemafibrate in Patients With Primary Biliary Cholangitis and Dyslipidemia: A Four-Year Analysis. (PubMed, Cureus) - "Background and aims Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease treated with ursodeoxycholic acid (UDCA), though some patients respond inadequately. This study evaluated the mid-term effects of pemafibrate on liver function and lipid profiles in PBC patients with dyslipidemia who were refractory to UDCA alone or with bezafibrate...Conclusions Pemafibrate with UDCA led to sustained liver enzyme improvement and was well-tolerated in dyslipidemic PBC patients refractory to standard therapy. Prospective studies are warranted to evaluate its long-term benefits, including in patients without dyslipidemia."

Journal • Dyslipidemia • Hepatology • Immunology • Metabolic Disorders • Primary Biliary Cholangitis

Selective PPARα Modulator (SPPARMα) in the Era of the MASLD Pandemic: Current Insights and Future Prospects. (PubMed, Yonago Acta Med) - "This review aims to summarize the therapeutic potential of SPPARMα in MASLD by examining the functional mechanisms of PPARα, preclinical studies in animal models, and accumulating clinical evidence from MASLD patients. Furthermore, we provide an overview of ongoing clinical trials investigating SPPARMα for MASLD treatment."

Journal • Review • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Treatment Resistant Patients with Metabolic Dysfunction-associated Steatohepatitis: Long-term Follow-up Prospective Study. (PubMed, JMA J) - "Primary treatment (weight control and medication of vitamin E and sodium-glucose cotransporter 2 inhibitor (SGLT2i)) was done and then pemafibrate treatment was added...The most effective treatment for patients with MASH could not be determined, according to the baseline levels of characteristics; however, weight control and step-by-step multidrug therapies made it possible to stabilize more than 90% of patient conditions and to solve MASH without worsening fibrosis. Since high levels of liver fibrosis-related markers affected the treatment resistance, MASH treatments should be started in an early stage while the levels of each marker are still low; type IV collagen <5.3 ng/mL, E value <13.7 kPa, FIB-4 index <1.89 and MASH fibrosis stage 2 or less."

Journal • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

A Phase 3 Study to Evaluate the Efficacy and Safety of K-877 in Chinese Patients With High TG and Low HDL-C (clinicaltrials.gov) - P3 | N=353 | Completed | Sponsor: Kowa Company, Ltd. | Recruiting ➔ Completed

Trial completion • Dyslipidemia

Study to Evaluate the Efficacy and Safety of K-808 (Pemafibrate) in Participants With Primary Biliary Cholangitis (PBC) With Inadequate Response to Ursodeoxycholic Acid (UDCA) and/or Obeticholic Acid (OCA) Treatment. (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Kowa Research Institute, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Immunology • Primary Biliary Cholangitis

Efficacy and Safety of Prolonged Treatment with Pemafibrate plus an HMG-CoA Reductase Inhibitor in Japanese Patients with Type 2 Diabetes Mellitus. (PubMed, Drug Res (Stuttg)) - "Similarly, improvement of the blood lipid profile without any adverse changes of the hepatic or renal function parameters was also observed in patients who received prolonged combined pemafibrate+statin treatment. Thus, our findings confirm the safety and efficacy of pemafibrate administered either alone or in combination with a statin."

Journal • Diabetes • Metabolic Disorders • Myositis • Type 2 Diabetes Mellitus

Effect of pemafibrate in reducing intestinal long-chain fatty acid absorption and hepatic fibrosis in metabolic dysfunction-associated steatohepatitis rats. (PubMed, BMC Gastroenterol) - "Pemafibrate reduced lipid droplet formation and LCFA absorption in the intestinal tract and alleviated hepatic fibrosis in MASH model rats."

Journal • Preclinical • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparison of the effects of pemafibrate and omega-3 fatty acid ethyl on fatty liver index in patients with dyslipidemia treated with statin: a sub-analysis from the PROUD48 study. (PubMed, Front Endocrinol (Lausanne)) - "The proportions of MASLD estimated by FLI (baseline/week 16) in PEMA and OMEGA-3 were 93.0/68.4% (P = 0.002) and 90.0/85.0% (P = 0.582), respectively. Pemafibrate is superior to omega-3 fatty acid ethyl in lowering effects of FLI and MASLD in patients with dyslipidemia receiving statin treatment, suggesting that pemafibrate is a beneficial agent for hypertriglyceridemia and reduction of the risk for MASLD."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • APOB

Competitive Ligand-Induced Recruitment of Coactivators to Specific PPARα/δ/γ Ligand-Binding Domains Revealed by Dual-Emission FRET and X-Ray Diffraction of Cocrystals. (PubMed, Antioxidants (Basel)) - "Single-FRET revealed that the respective PPARα/δ/γ-selective agonists (pemafibrate, seladelpar, and pioglitazone) induced the dissociation of the two corepressor peptides, NCoR1 and NCoR2, from the PPARα/δ/γ-LBDs and the recruitment of the two coactivator peptides, CBP and TRAP220. This illustrates that these coactivators bound to the same PPARα-LBD loci via their consensus LXXLL motifs in the liganded state; that NCoR1/NCoR2 corepressors bound to the same loci via the IXXXL sequences within their consensus LXXXIXXXL motifs in the unliganded state; and that ligand activation induced AF-2 helix 12 formation that interfered with corepressor binding and created a binding space for the coactivator. These PPARα/γ-related biochemical and physicochemical findings highlight the coregulator dynamics on limited PPARα/δ/γ-LBDs loci."

Journal • MED1 • NCOR1 • NCOR2 • PPARA • PPARG

A Study to Evaluate the Pharmacokinetics and Safety of K-808 (Pemafibrate) in Subjects With Primary Biliary Cholangitis With Compensated Cirrhosis and Without Cirrhosis. (clinicaltrials.gov) - P1 | N=17 | Completed | Sponsor: Kowa Research Institute, Inc. | Recruiting ➔ Completed

Trial completion • Fibrosis • Hepatology • Immunology • Primary Biliary Cholangitis

THREE-YEAR OUTCOMES UNDER PEMAFIBRATE THERAPY IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE: A LONG-TERM OBSERVATIONAL STUDY (DDW 2025) - "There was no combination use of sodium-glucose transport protein-2 inhibitor, pioglitazone or tocopherol. Three-year outcomes of pemafibrate therapy are favorable in patients with MASLD. Long-term pemafibrate therapy has a potential to prevent the progression of MASLD."

Clinical • Observational data • Diabetes • Dyslipidemia • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

THERAPEUTIC EFFECTS OF PEMAFIBRATE FOR PATIENTS WITH MASLD-REPORT OF TWO CASES WITH SERIAL LIVER BIOPSIES (DDW 2025) - "Serial liver biopsy showed pathologic improvement with results of NAS 3-0-0, Matteoni type 1, and Brunt G1S1. Conclusion; This is the first report of pathological improvement with pemafibrate in a patient with MASLD with high TG."

Biopsy • Clinical • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease

Pemafibrate improves liver biochemistry and GLOBE scores in patients with primary biliary cholangitis: Nationwide, multicenter study by the Japanese Red Cross Liver Study Group. (PubMed, Hepatol Res) - "In patients with PBC who showed an inadequate response to prior therapy, pemafibrate add-on or switch therapy improved liver biochemistry and GLOBE scores. Pemafibrate may be useful as a second-line drug when UDCA alone is inadequate, or as an alternative after combination therapy with other fibrates."

Clinical • Journal • Dyslipidemia • Hepatology • Immunology • Metabolic Disorders • Primary Biliary Cholangitis

Effects of Pemafibrate on Cardio-Ankle Vascular Index (CAVI) in Patients with Type 2 Diabetes or Ischemic Heart Disease: A 24-Week Observational Study. (PubMed, Vasc Health Risk Manag) - "While pemafibrate improves lipid profile and liver enzymes, its short-term impact on vascular stiffness, as measured by CAVI, appears limited. Extended follow-up studies are needed to clarify its cardiovascular benefits in high-risk patients."

Biomarker • Journal • Observational data • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Heart Failure • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • APOA1 • APOA2 • PPARA

Gut microbiota in patients with metabolic, dysfunction-associated steatotic liver disease. (PubMed, Curr Opin Clin Nutr Metab Care) - "Levels of harmful bacterial metabolites including ethanol, NH3, trimethylamine-L-oxide, 2-oleylglycerol, and litocholic acid are often increased in patients with MASLD. Conversely, short-chain fatty acids, indole derivatives, histidine, and the acids taurodeoxycholic, 3-succinylcholic, and hyodeoxycholic are decreased. The main aim of current interventions/treatments is to reduce harmful metabolites and increase beneficial ones. These interventions include drugs (pemafibrate, metformin, obeticholic acid), natural compounds (silymarin, lupeol, dietary fiber, peptides), exogenous bacteria (probiotics, gut symbionts), special diets (Mediterranean diet, time-restricted feeding), as well as microbiota transplantation, and phage therapy. Most improve gut permeability, liver inflammation, and fibrosis through microbiota regulation, and are promising alternatives for MASLFD management. However, most results come from animal studies, while clinical trials in MASLD patients are..."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor • Transplantation

Effects of Pemafibrate and Eicosapentaenoic Acid Ethyl Ester on Endothelial Function in Patients With Hypertriglyceridemia and Coronary Artery Disease: A Study Protocol for a Multicenter, Open-Label Randomised Controlled Trial. (PubMed, Cureus) - "This study investigates the comparative effects of pemafibrate and EPA on endothelial function, addressing an unmet need in managing residual cardiovascular risk in patients with CAD. The findings will contribute to the optimisation of treatment strategies in patients with CAD and hypertriglyceridemia."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia • PPARA