Rezdiffra (resmetirom) / Madrigal Pharma - LARVOL DELTA

Quick glance at 'metabolic dysfunction associated steatotic liver disease' therapeutics: Targets, trials, and trends. (PubMed, World J Gastrointest Pharmacol Ther) - "Resmetirom, a thyroid hormone receptor β (THR-β) agonist, is currently the lone agent approved for treating metabolic dysfunction-associated steatohepatitis (MASH). Off-label use of vitamin E and obeticholic acid has met with some treatment success...While metformin has largely failed to demonstrate efficacy, hepatotoxicity remains an area of concern with statin therapy...Despite encouraging advances, long-term safety, durability of response, and regulatory approvals remain key hurdles before these agents can be broadly implemented in clinical practice. This review summarizes current knowledge on the pathogenesis of MASLD/MASH and the molecular pathways that may offer therapeutic potential in managing this widespread metabolic liver disease."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Transplantation • Type 2 Diabetes Mellitus • FASN • SCD

SLC11A1 protein as a key regulator of iron metabolism, ferroptosis mediator, and putative therapeutic target in nonalcoholic fatty liver disease: an integrated bioinformatics analysis. (PubMed, Front Pharmacol) - "Molecular docking coupled with molecular dynamics simulations was employed to evaluate the binding patterns and dynamic stability of Resmetirom-a drug approved for the treatment of nonalcoholic fatty liver disease in adults-with the protein structures of ERN1 and SLC11A1...This study successfully identified specific proteins related to iron metabolism/ferroptosis pathways, such as ERN1 and SLC11A1, which demonstrate significant diagnostic potential for NAFLD, with SLC11A1 potentially possessing greater diagnostic value as a biomarker. The findings enhance the understanding of the genetically regulated pathogenesis of NAFLD and provide an important foundation for developing innovative diagnostic approaches and therapeutic interventions based on these targets."

Journal • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • ERN1 • PPARGC1A • SLC11A1 • TLR7

Meta-analysis of clinically available pharmacotherapy of biopsy confirmed metabolic dysfunction associated steatohepatitis (MASH). (PubMed, Diabetes Obes Metab) - "Clinically available medications are beneficial in reversing MASH. Improvements in RSw/oF and RFw/oS were greater at earlier stages of fibrosis. Future analyses of drug effects should include assessments adjusted for baseline study characteristics of Fibrosis Grades and may evaluate whether preventive therapy will have long term benefits if started at earlier stages of MASLD."

Journal • Retrospective data • Fibrosis • Hepatitis C • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis: A Narrative Review. (PubMed, Cureus) - "Its therapeutic potential was long realized, leading to the development of the first GLP-1 receptor agonist, exenatide, followed by liraglutide, dulaglutide, semaglutide, and tirzepatide...Alongside resmetirom, semaglutide is currently approved for the treatment of non-cirrhotic MASH with moderate-to-advanced fibrosis. Safety considerations include gastrointestinal intolerance, hypoglycemia, rare pancreaticobiliary events, and theoretical concerns of thyroid C-cell tumors, though human risk remains minimal. In summary, semaglutide extends the armamentarium of the hepatologist against the most common liver disease worldwide."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Hypoglycemia • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Thyroid Gland Carcinoma • Type 2 Diabetes Mellitus

Screening and management of metabolic dysfunction-associated steatotic liver disease (MASLD). (PubMed, JAAPA) - "It also provides guidance around use of resmetirom in primary care, reviewing the drug's indications, dosing, drug-drug interactions, and safety monitoring. Finally, it highlights semaglutide as an emerging treatment option for noncirrhotic MASH."

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

Optimized MASH Treatment Eligibility Cutoffs for MRE-measured Liver Stiffness and Proton Density Fat Fraction. (PubMed, Clin Mol Hepatol) - No abstract available

Journal • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Unravelling the reversion mechanisms of activated hepatic stellate cell properties by extracellular vesicles from mesenchymal stem cells. (PubMed, World J Stem Cells) - "Beyond resmetirom, a recently Food and Drug Administration-approved medication for liver fibrosis and nonalcoholic steatohepatitis, there are currently no other established pharmacological treatments available to slow down the progression of these conditions...However, detailed knowledge of the mechanisms involved in the alleviation of hepatic fibrosis using EVs from mesenchymal stem cells is still lacking. Hence, this review aims to describe the pathogenesis of hepatic fibrosis from the cellular and molecular point of views and shed light on the potential of EVs from mesenchymal stem cells in reversing the properties of aHSCs to their quiescent state."

Journal • Review • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Solid Tumor

A critical review of natural products driven correction of bile acid dysregulation: a therapeutic strategy for nonalcoholic fatty liver disease. (PubMed, Front Pharmacol) - "While two drugs (semaglutide, resmetirom) have recently been approved for nonalcoholic steatohepatitis (NASH), their clinical utility is constrained by gastrointestinal side effects, insufficient efficacy against fibrosis, and dose-related adverse events. Similarly, obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with antifibrotic potential, is associated with significant side effects, including severe pruritus...Future research must prioritize human-relevant models, large-scale randomized controlled trials (RCTs) with histological endpoints, and robust causal validation. By addressing these gaps, natural products targeting BA metabolism hold great promise to complement or replace existing therapies, offering safer and more effective personalized treatments for NAFLD."

Journal • Review • Dermatology • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pruritus • Transplantation

ANALYSIS OF MAESTRO-NASH, RESMETIROM RELATIVE TO PLACEBO PATIENTS, ON PRIMARY AND SECONDARY LIVER BIOPSY ENDPOINTS BASED ON ALIGNED BIOPSY ENDPOINTS AND STATISTICAL METHODS: FROM MASH CLINICAL TRIALS (AASLD 2025) - P3 | "Both RES and SEMA achieved both liver biopsy endpoints, improving NASH and liver fibrosis in the MN and ESS Phase 3 studies. Using an aligned statistical method, RES and SEMA showed 14-15% improvement of drug treatment relative to PBO in ≥1 stage fibrosis improvement at 1 and 1.5 years, respectively. RES and SEMA difference from PBO were 21% (3-fold relative to PBO) and 25% (2-fold relative to placebo), respectively, for NR requiring ≥2-pt NAS reduction."

Biopsy • Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Incepta launches first resmetirom medicine in Bangladesh (Business Standard)

Launch non-US • Metabolic Dysfunction-Associated Steatohepatitis

REZMASH: Resmiterom Efficacy & Safety in Patients With MASH (clinicaltrials.gov) - P4 | N=165 | Recruiting | Sponsor: Nabiqasim Industries (Pvt) Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Galmed Announces Grant of New Use Patents for the combination of Aramchol and Madrigal Pharmaceuticals' Rezdiffra (Resmetirom) for MASH (Galmed Pharma Press Release) - "The new patent granted in South Korea is added to earlier patents already granted by the United States Patent and Trademark Office (USPTO), Europe, Canada and other jurisdictions and will expire in the U.S. in July 2042....The patent covers the use of a combination therapy of Aramchol and Rezdiffra (MGL-3196, resmetirom) for the treatment of non-alcoholic steatohepatitis (NASH), also known as metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis in South Korea."

Patent • Metabolic Dysfunction-Associated Steatohepatitis

Targeting THR-β for MASLD: Mechanisms and Drug Development. (PubMed, Drug Des Devel Ther) - "Notably, Resmetirom, a selective THR-β agonist, gained FDA approval in 2024 for MASLD treatment, and several other THR-β agonists are currently undergoing preclinical or clinical studies...Therefore, further research is necessary to comprehensively assess their clinical efficacy and safety. This review summarizes the mechanisms by which TH/THR-β influences MASLD and recent advances in THR-β-targeted pharmacotherapy, aiming to enhance understanding of its therapeutic potential and promote drug development and clinical applications."

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

Discovery of a carboxyl fullerene derivative as a new lipid droplet regulator inhibiting MASLD. (PubMed, Gut) - "This study provides proof-of-concept supporting a nanoparticle-based agent as a LD homeostasis-targeted therapeutic to treat MASLD and related metabolic diseases."

Journal • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Leptin Receptor Deficiency Obesity • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • LEP • PLIN2

REZMASH: Resmiterom Efficacy & Safety in Patients With MASH (clinicaltrials.gov) - P4 | N=165 | Not yet recruiting | Sponsor: Nabiqasim Industries (Pvt) Ltd

New P4 trial • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Cost-Effectiveness of Resmetirom for Metabolic Dysfunction-Associated Steatohepatitis in Brazil. (PubMed, Value Health Reg Issues) - "Resmetirom was more effective than placebo but incurred higher costs. From the healthcare system perspective, it was not considered cost-effective under Brazil's conventional willingness-to-pay thresholds (1 to 3 times gross domestic product per capita per QALY) or thresholds based on opportunity cost. These findings underscore the need for caution in coverage and reimbursement decisions."

HEOR • Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Transplantation

Differences between therapeutic mechanisms of resmetirom and semaglutide against MASH in western diet-fed MC4R-knockout mice. (PubMed, Sci Rep) - "Similar to clinical evidence, semaglutide treatment, might cause muscle mass reduction due to food intake suppression. This is the first study to simultaneously compare the effects of resmetirom and semaglutide on MASH phenotypes and reveal the differences on their mechanisms of action in WD-fed MC4R-KO mice."

Journal • Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • MC4R

Oral Presentation: “Two-Year Time Course of Biomarker and Imaging Responses in Well-Compensated MASH Cirrhosis Patients Treated with Resmetirom” [Abstract #0167, Presenter: Naim Alkhouri] (GlobeNewswire) - "In this open-label analysis, Rezdiffra treatment for two years showed statistically significant improvements from baseline in multiple imaging and biomarker parameters in patients with compensated MASH cirrhosis (n=122; 113 completed two years of treatment). Improvements were also observed in a group of more advanced patients with platelet counts"

P3 data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Oral Presentation: “Improvement in Health-Related Quality of Life After Treatment with Resmetirom in Cirrhotic and Non-Cirrhotic Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Data from MAESTRO-NAFLD” [Abstract #0181, Presenter: Zobair Younossi] (GlobeNewswire) - "In a pooled analysis across the MAESTRO clinical program (n=1,323), patients treated with Rezdiffra reported significant and sustained improvements from baseline across multiple domains of the Liver Disease Quality of Life (LDQOL) and Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) – disease-specific tools assessing fatigue, worry, emotional function, and abdominal and systemic symptoms. Improvements were observed in both patients without cirrhosis and with compensated cirrhosis....In compensated MASH cirrhosis (n=180), by week 24 of treatment with Rezdiffra, worry and health distress improved, and were sustained by week 52 and throughout Year 2."

P3 data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Poster of Distinction: “Durability of Resmetirom Response in MASLD Patients After Two Years of Treatment in MAESTRO-NAFLD-OLE” [Abstract #4003, Presenter: Naim Alkhouri] (GlobeNewswire) - "When treatment resumed, improvements in MRI-PDFF, VCTE, and liver biochemistry were restored. In addition, patients who continued treatment for two years maintained consistent biomarker improvements, and those initially on placebo before entering the open-label extension achieved comparable benefits after switching to Rezdiffra. The therapy remained well tolerated, and transient gastrointestinal events did not generally recur after reinitiation."

P3 data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Determination and pharmacokinetic study of thyroid hormone receptor-β agonist resmetirom in beagle dogs using HPLC-MS/MS method. (PubMed, J Pharm Biomed Anal) - "Methanol-0.1 % formic acid was used as the mobile phase, resmetirom and carbamazepine (internal standard, IS) were separated on a VP-ODS C18 column. At the same time, resmetirom were stable under the experimental conditions. After oral administration of resmetirom to the beagle dogs, the Cmax of resmetirom was about 802.40 ng/mL at about 3.33 h, the t1/2 of resmetirom was about 4.58 h."

Journal • PK/PD data

Sagimet anticipates the data read out of its Phase 1 clinical trial to evaluate the PK and tolerability of a combination of denifanstat and resmetirom in the first half of 2026. (GlobeNewswire)

P1 data • Metabolic Dysfunction-Associated Steatohepatitis

Metabolic Dysfunction-Associated Steatotic Liver Disease in Adults: A Review. (PubMed, JAMA) - "It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis."

Journal • Cardiovascular • CNS Disorders • Dyslipidemia • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatic Encephalopathy • Hepatitis C • Hepatology • Hypertension • Immunology • Infectious Disease • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

Current Update on Nomenclature, Diagnosis, and Management of Metabolic Dysfunction-associated Steatotic Liver Disease: Radiologists' Perspective. (PubMed, Radiographics) - "Resmetirom has recently been approved for treating noncirrhotic adult patients with MASLD and moderate to severe hepatic fibrosis, along with diet and exercise...The article will serve as a reference for radiologists, who play a critical role in managing and prognosticating MASLD."

Journal • Review • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

An analysis of safety data from the first year of resmetirom. (PubMed, Gastroenterol Rep (Oxf)) - No abstract available

Journal