Parmodia (pemafibrate) / Kowa - LARVOL DELTA

Molecular Mechanisms and Clinical Evidence Supporting the Four Pillars of Therapy in Diabetic Kidney Disease: Emerging Therapeutic Perspectives. (PubMed, Int J Mol Sci) - "Imeglimin, pemafibrate, and dotinurad have similar chemical structures or effects to metformin, fibrates, and febuxostat, respectively, but are safer in patients with renal impairment. This article is a narrative review. Regarding emerging therapies for DKD, no high-evidence-level research has yet been published, and further progress in this area is warranted."

Journal • Review • Cardiovascular • Chronic Kidney Disease • Diabetes • Diabetic Nephropathy • Dyslipidemia • Hypertension • Metabolic Disorders • Nephrology • Renal Disease

A Convenient Laboratory-Scale Synthesis Route Toward the PPARα Agonist Pemafibrate. (PubMed, ChemistryOpen) - "In this work, convenient and high-yielding laboratory-scale procedures are presented for the synthesis of pemafibrate. With a primary focus on practicality and efficiency, literature and patent protocols were adapted, optimized, and combined to establish a new, straightforward, and efficient six-step synthetic route that starts from easily accessible and cheap substrates toward enantiopure pemafibrate at the multigram scale."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • PPARA

SELECTIVE PPARΑ MODULATOR INHIBITS CYST ENLARGEMENT IN ANIMAL MODEL OF POLYCYSTIC KIDNEY DISEASE. (ISN-WCN 2026) - "Although fenofibrate, a PPARα modulator, has been reported to suppress renal cysts enlargement, it has not yet been applied clinically due to concerns about renal metabolism and nephrotoxicity. RNA sequencing revealed pathway activity patterns characteristic of each tissue.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."

Preclinical • Autosomal Dominant Polycystic Kidney Disease • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • PPARA

PPARΑ MODULATOR PEMAFIBRATE AMELIORATES SALT-SENSITIVE HYPERTENSION AND HYPERTENSIVE ORGAN DAMAGE AFTER ISCHEMIA–REPERFUSION INJURY IN RATS (ISN-WCN 2026) - "Additionally, gene expression analysis revealed downregulation of inflammatory and fibrotic mediators, while nuclear translocation of PPARα was enhanced in tubular epithelial cells, consistent with transcriptional activation.Conclusion Pemafibrate, a selective PPARα modulator, ameliorates salt-sensitive hypertension and hypertensive kidney injury after IRI in rats by suppressing NLRP3-mediated inflammation, inhibiting NCC activation, and promoting CD86+CD163+ macrophage expansion. 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 • CD163 • CD68 • CD86 • IL1B • NLRP3 • PPARA

RATIONALE AND PROTOCOL OF THE JAPAN KIDNEY ASSOCIATION–PEMAFIBRATE INTERVENTION FOR CHRONIC KIDNEY DISEASE PATIENTS STUDY (JKAPI-CKD STUDY) (ISN-WCN 2026) - "The findings are expected to establish novel evidence for the treatment of hypertriglyceridemia with pemafibrate in patients with CKD. (Clinical trial registration: jRCTs031240097)I have potential conflict of interest to disclose.The JKAPI-CKD study is sponsored by Kowa Company LTD., with grant funding provided to the the Japan Kidney Association (JKA).I did not use generative AI and AI-assisted technologies in the writing process."

Clinical • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Hypertriglyceridemia • Nephrology • Renal Disease

A CASE OF LIPOPROTEIN GLOMERULOPATHY WITH APOE SENDAI VARIANT SUCCESSFULLY MAINTAINED WITHOUT PROGRESSION FOR EIGHT YEARS UNDER PEMAFIBRATE-BASED THERAPY (ISN-WCN 2026) - "Since proteinuria persisted, additional ARB, eicosapentaenoic acid (EPA), an SGLT2 inhibitor, and ezetimibe were introduced...Although bezafibrate has been reported to be effective in some cases, in this case, renal function had already declined at diagnosis, and bezafibrate was contraindicated. This is a rare case of LPG with APOE Sendai mutation in which renal function was preserved for eight years under pemafibrate-based therapy. Pemafibrate may represent a safe and effective treatment option for patients with LPG and renal impairment."

Clinical • Cardiovascular • Glomerulonephritis • Hematological Disorders • Ischemic stroke • Rare Diseases • Thrombosis • APOE

PPAR-α activator pemafibrate lowered plasma insulin-like growth factor-1 level in a patient with acromegaly. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Some in vitro studies have described beneficial effects of pemafibrate. Pemafibrate warrants investigation as a new treatment for acromegaly."

Journal • Acromegaly • Dyslipidemia • Endocrine Disorders • Metabolic Disorders • IGF1

Managing metabolic risks in coronary artery disease: A scoping review of recent clinical and therapeutic evidence. (PubMed, J Diabetes Metab Disord) - "Pharmacologic interventions such as SGLT2 inhibitors, GLP-1 receptor agonists, pemafibrate, and Rho-kinase inhibitors showed consistent improvements in metabolic and cardiovascular parameters...A shift toward precision cardiometabolic care-combining biomarker-driven diagnostics, sustained lifestyle modification, and individualized pharmacotherapy is essential. Future multicentric trials and digital health innovations should address persistent evidence and practice gaps, especially within high-risk Asian and Indian populations."

Journal • Review • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Genetic Disorders • Hypertension • Metabolic Disorders • Obesity

The Clarity Trial: Prospective evaluation of pemafibrate therapy in MASLD (APASL 2026) - No abstract available

Clinical • Metabolic Dysfunction-Associated Steatotic Liver Disease

Antifibrotic Efficacy and Renal Safety of Pemafibrate in MASLD: A Multicenter Randomized Controlled Study (APASL 2026) - No abstract available

Clinical • Metabolic Dysfunction-Associated Steatotic Liver Disease

Pemafibrate attenuates liver fibrosis and reduces predicted gut lipopolysaccharide biosynthesis and mucin degradation in a metabolic dysfunction-associated steatohepatitis rat model (EASL 2026) - No abstract available

Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Dose-dependent efficacy and renal safety of pemafibrate in patients with MASLD: a multicenter randomized controlled trial (EASL 2026) - No abstract available

Clinical • Metabolic Dysfunction-Associated Steatotic Liver Disease

Hepatic molecular pathways associated with pemafibrate treatment in a rat model of metabolic-associated steatotic liver disease (EASL 2026) - No abstract available

Preclinical • Hepatology

Effects of pemafibrate on liver fibrosis in patients with MASLD and hypertriglyceridemia: A 2-year retrospective observational study using MR elastography. (PubMed, J Clin Lipidol) - "Two-year pemafibrate treatment significantly improved liver stiffness and hepatic parameters independent of weight loss or fat reduction, indicating potential antifibrotic mechanisms. These real-world findings support the hepatoprotective role of pemafibrate and warrant validation in prospective trials."

Journal • Observational data • Retrospective data • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

TRIM28 Is an E3 Ligase of IRP2 Suppressing Ischemia/Reperfusion-Induced Myocardial Ferroptosis. (PubMed, Circulation) - "To explore the function of TRIM28, we used adeno-associated virus serotype 9 to achieve cardiomyocyte-specific overexpression and generated tamoxifen-inducible cardiomyocyte-specific TRIM28 knockout mice...Mechanistically, TRIM28 functioned as an E3 ubiquitin ligase that directly bound to IRP2 (iron regulatory protein 2) and promoted K48-linked ubiquitination at the K877 site, leading to the downregulation of IRP2 and TFR1 (transferrin receptor 1), suppression of intracellular iron uptake, and consequent attenuation of cardiomyocyte ferroptosis...Last, we demonstrated that perhexiline inhibited I/R-induced myocardial ferroptosis by upregulating p55γ and TRIM28. Our study identifies TRIM28 as an essential E3 ubiquitin ligase of IRP2 and delineate TRIM28-mediated inhibition of myocardial ferroptosis by targeting IRP2-TFR1 signaling protects the heart against I/R injury, indicating that targeting TRIM28 represents a promising therapeutic strategy for suppressing..."

Journal • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Myocardial Ischemia • Reperfusion Injury • Targeted Protein Degradation • TFRC • TRIM28

Comparative effectiveness of pemafibrate versus bezafibrate on hepatic and vascular endothelial function in patients with coronary artery disease and metabolic dysfunction-associated steatotic liver disease. (PubMed, Front Endocrinol (Lausanne)) - "Both treatments significantly lowered HOMA-IR; however, the decrease was similar between the groups (P = 0.724). Pemafibrate is more effective than bezafibrate at reducing ALT levels while offering similar beneficial effects on insulin resistance and endothelial function in CAD patients with MASLD."

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

Reversibly reduced lipoprotein lipase in APOA5 c.553G>T-related hypertriglyceridemia successfully treated with pemafibrate. (PubMed, Endocrinol Diabetes Metab Case Rep) - "Pemafibrate may improve both LPL levels and lipid profiles, even in cases with reduced LPL protein and chylomicronemia. ApoA5-related chylomicronemia can resemble familial chylomicronemia syndrome but may respond to therapies such as pemafibrate, highlighting the importance of accurate genetic diagnosis."

Journal • Diabetes • Dyslipidemia • Endocrine Disorders • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders • Severe Hypertriglyceridemia • APOA5 • LPL • PPARA

Design, synthesis and activity evaluation of a novel PPARα agonist based on virtual screening. (PubMed, Bioorg Med Chem Lett) - "To discover novel scaffold agonists, we used Pemafibrate as a template to construct a focused chemical library with the infiniSee software...Notably, XYQ3-B11 possesses a distinctive hybrid architecture, comprising a central pyridine ring, a 2-fluorobenzoate moiety, and an indole-derived side chain. These findings highlight XYQ3-B11 as a promising novel chemotype for the start of development of PPARα agonists."

Journal • Dyslipidemia • Metabolic Disorders • PPARA

Crossover Trial of Pemafibrate and Omega-3-Acid Ethyl Esters for Hypertriglyceridemia in Patients with Cardiovascular Disease. (PubMed, JMA J) - "Pemafibrate may be an effective first choice for hypertriglyceridemia, and add-on DHA+EPA may be beneficial when pemafibrate is not sufficiently effective. Findings need to be confirmed in larger studies."

Journal • Cardiovascular • Dyslipidemia • Fibrosis • Hypertriglyceridemia • Immunology • Metabolic Disorders

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

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

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