Rezdiffra (resmetirom) / Madrigal Pharma - LARVOL DELTA

A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES) (clinicaltrials.gov) - P3 | N=700 | Active, not recruiting | Sponsor: Madrigal Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Immunopathogenic mechanisms and immunoregulatory therapies in MASLD. (PubMed, Cell Mol Immunol) - "Current therapies for MASH, including the recently approved thyroid hormone receptor-beta agonist resmetirom or the available incretin mimetics, mainly target metabolic injury to the liver but not inflammation directly. In this review, we provide an in-depth discussion of current data related to the immunological mechanisms of MASLD and summarize the effects of current and experimental therapies on immunoregulation in MASLD."

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

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Efficacy and Safety of Resmetirom in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ENDO 2025) - "Resmetirom demonstrates promising efficacy in the treatment of MASLD, significantly reducing MRI-PDFF, LDL-C, triglycerides, lipoproteins, and liver enzymes, with no major safety concerns."

Retrospective data • Review • Cardiovascular • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Comparative Efficacy and Safety of Resmetirom vs Efruxifermin for Metabolic Dysfunction-Associated Steatohepatitis: A Network Meta-Analysis of Randomized Controlled Trials (ENDO 2025) - "Both Resmetirom and Efruxifermin demonstrate significant efficacy in reducing hepatic fat fraction and ALT levels in MASH patients. Resmetirom showed a slightly greater effect on hepatic fat reduction and a more favorable safety profile. These findings highlight Resmetirom as a potentially superior first-line therapy for MASH, though individual patient characteristics and treatment tolerability should guide clinical decisions."

Retrospective data • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor • FGF21

Lights and Shadows of a Vegetarian Diet in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease. (PubMed, Nutrients) - "Despite the recent Food and Drug Administration (FDA) approval of Resmetirom as the first drug for patients with Metabolic dysfunction-associated steatohepatitis (MASH) and significant fibrosis, and several ongoing clinical trials, lifestyle changes aimed at achieving sustained weight loss remain a cornerstone in the management of these patients...Several studies have demonstrated the benefits of the Mediterranean diet in this regard, and there is also emerging evidence on the vegetarian diet and its different patterns. This review aims to summarize the currently available evidence on the potential benefits of a vegetarian diet in patients with MASLD, as well as exploring its potential limitations."

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

Three Neglected STARD Criteria Reduce the Uncertainty of the Liver Fibrosis Biomarker FibroTest-T2D in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). (PubMed, Diagnostics (Basel)) - "Background/Objectives: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis tests in patients with metabolic liver disease (MASLD)...FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance."

Biomarker • Journal • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus • APOA1 • HP

Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024. (PubMed, Pharmaceuticals (Basel)) - "Notably, eight of these drugs (including Rezdiffra®, Voydeya®, Iqirvo®, Voranigo®, Livdelzi®, Miplyffa®, Revuforj®, and Crenessity®) are classified as "first-in-class" and have received breakthrough therapy designation. These agents not only exhibit distinct mechanisms of action but also offer substantial improvements in efficacy for patients compared to prior therapeutic options. This article offers a comprehensive analysis of the mechanisms of action, clinical trials, drug design, and synthetic methodologies related to representative drugs, aiming to provide crucial insights for future pharmaceutical development."

FDA event • Journal • Review • Alopecia • Brain Cancer • Breast Cancer • Cardiovascular • Chronic Kidney Disease • Chronic Obstructive Pulmonary Disease • CNS Disorders • Congenital Adrenal Hyperplasia • Cystic Fibrosis • Dermatology • Duchenne Muscular Dystrophy • Endocrine Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders • Glioma • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertension • Immunology • Infectious Disease • Leukemia • Lung Cancer • Lysosomal Storage Diseases • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Muscular Dystrophy • Nephrology • Non Small Cell Lung Cancer • Oncology • Primary Biliary Cholangitis • Psychiatry • Pulmonary Disease • Renal Disease • Respiratory Diseases • Schizophrenia • Solid Tumor • Ventricular Tachycardia

Effect of Resmetirom or Placebo in Nash (mash) fibrosis patient with ≥ 5% Weight Loss and/Or on Baseline GLP-1 therapy in the Maestro-Nah 52-Week Serial Liver Biopsy Study (DDG 2025) - P3 | "Stable GLP-1 Therapy Did not impact Liver Biopsy Endpoints or Cause Weight Loss. In the placebo Group, Stable GLP-1 Therapy Did not Result in Weight Loss, and Biopsy Response Rates in GLP-Treated Placebo Patients Were Similar or Slightly Lower Than Placebo Patients Not on GLP Therapy."

Biopsy • Clinical • Diabetes

Assessment of Resmetirom Efficacy (80 mg vs. 100 mg) Stratified by Baseline Body Mass Index and Weight in Patients from the Maestro-Nos Trial (DDG 2025) - P3 | "as shown in thesis stratified data, resmetirom 100 mg was consistently more effective than 80 mg in achievement of the dual primary endpoints in the sample of patients who had high higher baseline body weight and bmi. In Patients with a Lower BMI, there was no obeded difference in efficacy between the 80 and 100 mg resmetirom dose."

Clinical • Diabetes

Sagimet Biosciences to Host Virtual KOL Event, “Evaluating the Synergistic Potential of a Combination of Denifanstat and Resmetirom for the Treatment of Metabolic Dysfunction-Associated Steatohepatitis (MASH)” on May 29, 2025 (GlobeNewswire) - "The event will provide an overview of the planned Phase 1 pharmacokinetic clinical trial of the denifanstat and resmetirom combination, and a discussion on the potential benefits of combination therapy to treat patients living with advanced MASH."

Clinical • Metabolic Dysfunction-Associated Steatohepatitis

LEADS - a comprehensive human liver-on-a-chip for non-alcoholic steatohepatitis (NASH) drug testing. (PubMed, Lab Chip) - "Notably, treatment with saroglitazar, pioglitazone, cenicriviroc (CVC), obeticholic acid (OCA) and resmetirom produced responses similar to those observed in clinical trials. Taken together, our LEADS model is the first model developed using patient-derived hepatic stem cells which recapitulated all key features used for comprehensive drug testing, with results matching to clinical responses."

Journal • Fibrosis • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Oncology • Solid Tumor

The Role of Invasive Diagnostics in Prior Authorization for MASH (ISPOR 2025) - " PA criteria for resmetirom, approved for NASH with moderate to advanced liver fibrosis, were reviewed focusing on requirements such as liver biopsy, stages of liver fibrosis, and metabolic risk factors... Our findings indicate that 3/5 reviewed plans do not mandate liver biopsy as a PA requirement, despite its use in clinical trials. This reflects a growing emphasis on balancing diagnostic accuracy with patient safety and accessibility. These findings highlight a divergence from clinical trial requirements, with payer criteria aligning more closely with real-world practices to reduce procedural risks and barriers to care."

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

Non-Invasive Tests (NITs) to Risk-Stratify Patients with Noncirrhotic Metabolic-Associated Steatohepatitis (MASH) in a Specialty Setting Eligible for Resmetirom: A Cost-Effectiveness Analysis from a U.S. Payer Perspective (ISPOR 2025) - "This modeling study demonstrates that imaging-based NITs without LB offer the most cost-effective approach for diagnosing F2-F3 MASH in the US, while enhancing diagnostic efficiency and reducing reliance on invasive and costly LBs. These findings highlight the value of integrating NIT-only strategies to enhance access to emerging therapies, support payer value, and optimize healthcare resources."

Clinical • Cost effectiveness • HEOR • Non-invasive • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Evaluating Resmetirom Eligibility Among Patients with MASH: Insights from the German Steatotic Liver Disease-Registry. (PubMed, Z Gastroenterol) - "Using VCTE 8-15 kPa results in 182 (28.5%) eligible patients.Eligibility for resmetirom treatment depends on the available method used to identify "at-risk MASH". Availability of VCTE was highest among different levels of care."

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

4200: SOA - Update on MASLD Therapies Pipeline (DDW 2025) - "Description: This State-of-the-Art session provides a timely update on the evolving MASLD therapies pipeline, featuring insights into emerging pharmacologic agents and real-world data on current treatments. Topics include the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes, eligibility criteria for resmetirom therapy, and phase 2 results for efimosfermin alfa in MASH with fibrosis.Learning Objectives:• Describe the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes• Identify the eligibility criteria for resmetirom therapy• Discuss phase 2 results for efimosfermin alfa in MASH with fibrosis"

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

Determining Cirrhosis Status in Candidates for Resmetirom. (PubMed, Clin Gastroenterol Hepatol) - No abstract available

Journal • Fibrosis • Immunology

Madrigal Announces New Clinical Data Demonstrating Rezdiffra (resmetirom) Significantly Improved Multiple Noninvasive Tests and Portal Hypertension Risk in Patients with Compensated MASH Cirrhosis (GlobeNewswire) - P3 | N=1,343 | MAESTRO-NAFLD1 (NCT04197479) | Sponsor: Madrigal Pharmaceuticals, Inc. | "Madrigal Pharmaceuticals, Inc...announced positive two-year results from the open-label compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial of Rezdiffra....Among patients with CSPH at baseline, 65% moved into lower risk categories by year two (42% to no/low CSPH and 23% to probable CSPH). Among patients with probable CSPH at baseline, 57% moved into the no/low CSPH category as compared to 14% who moved into the CSPH category by year two. Improvement in CSPH risk was statistically significant compared to baseline....At 8 a.m. EDT May 13, 2025, Madrigal will host a webcast to review the detailed two-year data from the compensated MASH cirrhosis (F4c) arm of the Phase 3 MAESTRO-NAFLD-1 trial."

P3 data • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Thyroid dysfunction in MASLD: Results of a nationwide study. (PubMed, JHEP Rep) - "The approval by the US FDA of resmetirom, a thyroid hormone receptor β-selective agonist for non-cirrhotic metabolic dysfunction-associated steatohepatitis with stage 2-3 fibrosis, highlights the potential role of thyroid dysfunction in metabolic-associated steatotic liver disease (MASLD)...Hyperthyroidism was potentially inversely associated with MASLD. Despite its low prevalence (2.5% in MASLD cases, 1.4% in controls), the population health impact of hypothyroidism warrants further attention."

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

Resmetirom as an important cornerstone of multidisciplinary management of metabolic dysfunction-associated steatohepatitis. (PubMed, Hepatobiliary Surg Nutr) - No abstract available

Journal • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Metabolic, skeletal, and cartilage effects of a high-fat diet and the therapeutic impact of MGL3196 are age- and sex-dependent in mice. (PubMed, Bone) - "Additionally, measurements of articular cartilage indicated that MGL treatment reduced articular cartilage degradation in both sexes, which was attributed to aging and a HFD. Our findings suggest tailored therapies are necessary to address the adverse effects of a HFD on fat, bone, and cartilage metabolism, specifically considering factors such as age and sex."

Journal • Preclinical • Diabetes • Hepatitis B • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Osteoarthritis • Osteoporosis • Pain • Rheumatology • Type 2 Diabetes Mellitus

13170: Clinical Deep Dive: Unlocking the Treatment Potential of Rezdiffra (DDW 2025) - "Supported by: Madrigal Pharmaceuticals Description: Please join us for an engaging and highly anticipated educational panel focusing on Rezdiffra and it's clinical data."

Clinical

CLINICAL DEEP DIVE: UNLOCKING THE TREATMENT POTENTIAL OF REZDIFFRA (DDW 2025) - "Supported by: Madrigal Pharmaceuticals"

Clinical

ELIGIBILITY FOR RESMETIROM THERAPY USING VIBRATION-CONTROLLED TRANSIENT ELASTOGRAPHY: A COMPARATIVE ANALYSIS OF EXPERT PANEL AND AASLD RECOMMENDATIONS (DDW 2025) - No abstract available

Metabolic Dysfunction-Associated Steatotic Liver Disease