Parmodia (pemafibrate) / Kowa - LARVOL DELTA

Sexual dimorphism of Sprague-Dawley rats in the liver inflammatory/fibrotic response to a high in sucrose and fat, choline-deficient, L-amino acid CDAA diet (EASL 2025) - "Background and Aims: We have shown the efficacy and security of bempedoic acid and pemafibrate in an experimental model of simple metabolic dysfunction-associated steatotic liver in Sprague-Dawley (SD) rat (Biomedicines 10 (2022) 1517, Biomed&Pharmacother 177 (2024) 117067). There is a clear sexual dimorphism in the response of SD rats to a CDAA diet, with males developing MASH after three months of continuous CDAA diet supplementation, while females not showing any clear increase in liver fibrotic markers after five months of CCDA diet supplementation."

Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • ACTA2 • COL1A1 • GDF15 • IL1B • IL6 • TGFB1 • TIMP1 • TNFA

Anti-steatosis effect of telmisartan in a MASL-dietary rat model does not associates to changes in faecal bile acid metabolome (EASL 2025) - "Background and Aims: We have previously shown that pemafibrate administration prevents steatosis development in an experimental model of simple metabolic-associated steatotic liver disease (MASL) in Sprague-Dawley (SD) rat (Biomed&Pharmacother 177 (2024) 117067), further inducing significant changes in faecal bile acid (BA) metabolome...The concentrations of 10 BA (cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid, ursodeoxycholic acid, α-muricholic acid, β- muricholic acid, hyocholic acid, hyodeoxycholic acid, and murideoxycholic acid) in rat faeces were determined by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS), as described previously (Biomed&Pharmacother 177 (2024) 117067)... Anti-steatosis effect of Telmisartan in a SD rat MASL dietary model do not associate with significant changes in faecal BA metabolome."

Preclinical • Hepatology

EFFECTS OF PEMAFIBRATE VERSUS BEZAFIBRATE ON LIVER AND VASCULAR ENDOTHELIAL FUNCTION IN PATIENTS WITH CORONARY ARTERY DISEASE AND METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE - Akihiro Nakamura (ACC 2025) - "Compared to bezafibrate, pemafibrate is more effective in reducing ALT and γGT levels while having similar beneficial effects on insulin resistance and endothelial function in CAD patients with MASLD."

Clinical • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

CHANGES IN APOLIPOPROTEIN B AND LOW-DENSITY LIPOPROTEIN CHOLESTEROL AND CARDIOVASCULAR EVENTS WITH PEMAFIBRATE THERAPY - Brendan Everett (ACC 2025) - "In this analysis of post-randomization on-treatment levels of apoB and LDL-C, elevations in apoB or LDL-C in patients on active pemafibrate did not associate with differences in CV outcomes compared to placebo."

Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

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 Provisionally accepted (Frontiers) - P=N/A | N=57 | jRCTs071200011 | "Results: Median FLI was significantly decreased by both PEMA (69.7 to 47.6, P < 0.001) and OMEGA-3 (64.8 to 59.5, P < 0.001). There was a significant difference in change in FLI between PEMA and OMEGA-3 (-18.3 ± 14.1 vs. -5.5 ± 9.4, P < 0.001). 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.Conclusions: 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 data • Dyslipidemia • Metabolic Dysfunction-Associated Steatotic Liver Disease

Predictive Factors for the Therapeutic Effect of Pemafibrate in MASLD Patients (APASL 2025) - "In the MetALD/ALD group, TG and liver damage persisted after pemafibrate administration compared to the MASLD group. Evaluating alcohol consumption before treatment may help prediction of the therapeutic effect."

Biomarker • Clinical • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Pemafibrate modulates peroxisome proliferator-activated receptor alpha and prevents alcohol-associated liver disease (APASL 2025) - "The results of the present study demonstrated that pemafibrate modulates target genes related to hepatic lipid metabolism and prevents deposition of fat globules in the liver during chronic alcohol feeding in rats. Therefore, pemafibrate could be used as a potent therapeutic agent to prevent steatosis and related adverse events in ALD. Email: georgej@kanazawa-med.ac.jp"

Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • PPARA

Remnant Cholesterol: Should it be a Target for Prevention of ASCVD? (PubMed, Curr Atheroscler Rep) - "Most recently, the PROMINENT trial failed to show a beneficial effect of 0.4 mg/day of pemafibrate on the risk of ASCVD...Further trials are warranted to ascertain the efficacy of novel remnant cholesterol- and triglyceride-lowering agents in the prevention of ASCVD. To reduce ASCVD, active agents need to reduce total atherogenic cholesterol (LDL and remnant cholesterol) and apolipoprotein B."

Journal • Review • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Heart Failure • APOB

Managing Dyslipidemia in Chronic Kidney Disease: Implications for Cardiovascular and Renal Risk. (PubMed, Curr Atheroscler Rep) - "Emerging lipid-lowering agents, including bempedoic acid, pemafibrate, and PCSK9 inhibitors, show promise for risk reduction, especially in non-dialysis-dependent CKD. The advent of novel therapeutic options and a deeper understanding of dyslipidemia's pathophysiology hold potential for improving outcomes. Future research should prioritize personalized approaches, focusing on the unique metabolic derangements of CKD and advancing treatments for high-risk and dialysis-dependent patients."

Biomarker • Journal • Review • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular Disease: Is There Still Room? (PubMed, Curr Atheroscler Rep) - "This review examines the role of fibrates and the selective PPAR-alpha modulators (SPPARM-α), pemafibrate, in diabetic microvascular disease...Their benefits in reducing microvascular damage support their broader adoption in clinical practice. However, additional dedicated randomized trials are essential to validate the efficacy of those agents in contemporary diabetes care era and to address the growing burden of diabetes-related microvascular complications."

Journal • Review • Cardiovascular • Diabetes • Metabolic Disorders • Pain • Peripheral Arterial Disease • Renal Disease • Retinal Disorders

Effectiveness of Pemafibrate in Improving TG and ALT Levels in Fatty Liver with Hypertriglyceridemia (APASL 2025) - No abstract available

Dyslipidemia • Hypertriglyceridemia

THREE-YEAR OUTCOMES UNDER PEMAFIBRATE THERAPY IN PATIENTS WITH METABOLIC DYSFUNCTION-ASSOCIATED STEATOTIC LIVER DISEASE: A LONG-TERM OBSERVATIONAL STUDY (DDW 2025) - No abstract available

Clinical • Observational data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

THERAPEUTIC EFFECTS OF PEMAFIBRATE FOR PATIENTS WITH MASLD-REPORT OF TWO CASES WITH SERIAL LIVER BIOPSIES (DDW 2025) - No abstract available

Biopsy • Clinical • Metabolic Dysfunction-Associated Steatotic Liver Disease

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 | Recruiting | Sponsor: Kowa Research Institute, Inc. | Trial completion date: Apr 2026 ➔ Aug 2026 | Trial primary completion date: Apr 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Hepatology • Immunology • Primary Biliary Cholangitis

Effectiveness of Pemafibrate Dose Escalation on Metabolic Dysfunction-Associated Steatotic Liver Disease Refractory to Standard Dose. (PubMed, Metabolites) - "The lipid profiles, the albumin-bilirubin score, and M2BPGi did not significantly change after the dose escalation. The dose escalation of pemafibrate from 0.2 mg to 0.4 mg daily may improve hepatic inflammation in patients with MASLD refractory to standard-dose therapy."

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

Effect and safety of pemafibrate for patients with type 2 diabetes mellitus and hypertriglyceridemia: a retrospective analysis of clinical data. (PubMed, BMC Endocr Disord) - "PEMA showed beneficial effects on lipid metabolism and liver function. The improvement of lipid metabolism was found in patients switching from other fibrates. It is possible that PEMA may improve lipid metabolism in patients with hypertriglyceridemia."

Clinical data • Journal • Retrospective data • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Unique Liquid Chromatography Technique for Determining a New Selective PPARα Modulator Drug (Pemafibrate) in the Tablet Dosage Form, Robustness by Design Expert in the Light of Quality by Design. (PubMed, Biomed Chromatogr) - "Precision results showed %RSD values of 1.0 and 1.1. Forced degradation studies indicated sensitivity to acid hydrolysis stress conditions and stability under physical stress conditions."

Journal • PPARA

Peroxisome proliferator-activated receptor alpha is an essential factor in enhanced macrophage immune function induced by angiotensin-converting enzyme. (PubMed, Cell Mol Immunol) - "With pemafibrate, the number of antitumor CD8+ T cells was significantly lower in A10-PPARα-Cre mice than in ACE10/10 mice. We conclude that PPARα is important in the immune system of myeloid cells, including wild-type cells, and that its increased expression by ACE-expressing macrophages in ACE10/10 mice is indispensable for ACE-dependent functional upregulation of macrophages in both mice and human cells."

Journal • Infectious Disease • Metabolic Disorders • Oncology • CD8 • PPARA

PPARα-ERRα crosstalk mitigates metabolic dysfunction-associated steatotic liver disease progression. (PubMed, Metabolism) - "Our study supports that dual nuclear receptor targeting, which simultaneously increases PPARα and diminishes ERRα activity, may represent a viable novel strategy against MASLD."

Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • ESRRA • PPARA • SAA1

Pemafibrate ameliorates renal injury through induction of FGF21 and ketone body production in male mice. (PubMed, Physiol Rep) - "Treatment of proximal tubular cells with FGF21 or BHB reduced expression of epithelial-mesenchymal transition markers. These findings suggest that pemafibrate could ameliorate renal damage, at least in part, by its abilities to increase the production of FGF21 and BHB."

Journal • Preclinical • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • FGF21 • PPARA

A Significant Effect of Pemafibrate on Carotid and Cerebral Atherosclerosis in Patients with Hypertriglyceridemia and Stroke. (PubMed, J Atheroscler Thromb) - No abstract available

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia

Regulation of UCP1 expression by PPARα and pemafibrate in human beige adipocytes. (PubMed, Life Sci) - "Conversion of white into thermogenic adipocytes is mainly due to the activation of PPARγ. Moreover, we show that PPARα seems to act as a hindrance for PPARγ-dependent beiging. Our data question the role of PPARα in human adipocyte browning and the specificity of pemafibrate in adipocytes."

Journal • PPARA • PPARG

Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia. (PubMed, Expert Opin Pharmacother) - "These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3)...Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia and other ANGPTL3 inhibitors may prove be useful to reduce triglycerides in T2D."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ANGPTL3

Evaluation of the beneficial effects of pemafibrate in hypertriglyceridemia with or without alcohol drinking (PAR-CHAT: PARmodia-CHikushi Anti-dyslipidemia Trial). (PubMed, Int J Cardiol Cardiovasc Risk Prev) - "Pemafibrate improves TG, HDL-C, hepatic biomarkers and hypertriglyceridemia regardless of alcohol consumption and is safe. Increase of LDL-C was suppressed in patients treated with statins."

Journal • Addiction (Opioid and Alcohol) • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders

Usefulness of pemafibrate for non-alcoholic fatty liver disease with hypertriglyceridemia. (PubMed, Clin Exp Hepatol) - "Most of these improvements remained after six months. Oral pemafibrate treatment improved NAFLD in patients with hypertriglyceridemia, indicating that pemafibrate may be a new treatment option for NAFLD."

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