efruxifermin (NN9062) / Amgen, Novo Nordisk - LARVOL DELTA

Comparative Efficacy and Safety of FGF21 Analogues in MASH: Which Agents Are Advancing and Why? (ACG 2026) - "Introduction: Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of progressive liver fibrosis and cirrhosis... A structured literature review of PubMed/MEDLINE was conducted through April 2026 using keywords and MeSH terms including âMASH,â âNASH,â âfibroblast growth factor 21,â âFGF21 analogues,â âefruxifermin,â âpegozafermin,â âefimosfermin,â âpegbelfermin,â âresmetirom,â âsemaglutide,â âtirzepatide,â âsurvodutide,â âlanifibranor,â and âclinical trial.â Included studies were randomized controlled trials in biopsy-confirmed MASH or MASLD reporting histologic data...Trials of pegbelfermin and MK-3655 did not meet primary endpoints... Twelve trials (N=3,640) were included. Among FGF21 analogues, efruxifermin 50 mg showed the greatest response, with fibrosis improvement up to 75% and MASH resolution up to 62%..."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Histologic and Metabolic Efficacy of Efruxifermin in Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Systematic Review and Meta-Analysis (ACG 2026) - "Across the six included RCTs, the outcome-specific pooled population varied due to differing biopsy availability and follow-up durations. Compared with placebo, EFX significantly improved fibrosis by â¥1 stage without worsening of MASH (RR 2.20; 95% CI 1.34-3.63) and increased the likelihood of MASH resolution without worsening of fibrosis (RR 2.82; 95% CI 1.78-4.48). EFX was also associated with greater improvement in ALT levels (RR 3.16; 95% CI 1.24-8.06)."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Efficacy of Efruxifermin on Liver Injury Biomarkers Across the MASLD/MASH Spectrum: A Meta-analysis of Randomized Controlled Trials (ACG 2026) - "Across 4 randomized trials, Efruxifermin favored improvement in all pooled biomarker outcomes. In all-stage analyses, pooled effects were: ELF score, MD -0.718 (95% CI, -0.861 to -0.574); Pro-C3, SMD -4.510 (-5.065 to -3.954); ALT, MD -15.692 U/L (-23.392 to -7.992); AST, MD -12.448 U/L (-18.125 to -6.771); GGT, MD -24.672 U/L (-34.427 to -14.918); ALP, MD -8.269 U/L (-12.365 to -4.174); and urate, MD -0.609 mg/dL (-0.769 to -0.448). Heterogeneity was low for ELF, GGT, ALP, and urate, moderate for AST and Pro-C3, and highest for ALT, consistent with biologic differences across fibrosis stages."

Biomarker • Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Comparative Efficacy of Pharmacological Agents for Metabolic Dysfunction-Associated Steatohepatitis: An Updated Network Meta-Analysis (ACG 2026) - "Fourteen treatment arms (n=3,417) were included for steatohepatitis resolution and 17 treatment arms (n=4,329) for fibrosis improvement across trials ranging from 24-96 weeks. Tirzepatide 15 mg showed the highest overall efficacy (OR 14.3), while semaglutide 2.4 mg (OR 3.3) and resmetirom 100 mg (OR 4.0) demonstrated significant benefit in Phase 3 trials. Efruxifermin 50 mg ranked highly for steatohepatitis resolution, whereas dapagliflozin 10 mg showed favorable antifibrotic effects (OR 3.3) in recent studies."

Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Efruxifermin in MASH With F2/F3 Fibrosis: Post Hoc Analysis Indicated Early Histologic Features of Regression Were Associated with Week 96 Fibrosis Improvement (ACG 2026) - P2 | "More participants in the efruxifermin groups than placebo had improvements in 4-6 features of regression at the early timepoint of week 24 (Table). In the efruxifermin group, an increase in the number of regression features from baseline to week 24 was generally associated with higher rates of week 96 histological response, defined as improvement in â¥1 stage and no worsening of MASH. Participants with early improvements in more regression features from baseline also had numerically larger improvements in noninvasive fibrosis measures at week 96."

Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Resmetirom Versus Semaglutide 2.4 Mg and Emerging Agents for MASH: A Network Meta-Analysis Enabling the First Indirect Comparison of FDA-Approved Therapies (ACG 2026) - "Efruxifermin 50 mg achieved the greatest liver fat reduction (MD â57.70 percentage points). Twenty-two RCTs encompassing 38 interventions were included. In Phase 2 data, tirzepatide 15 mg ranked highest for MASH resolution (RR 0.17, 95% CI 0.07â0.39; P-score 0.853) and fibrosis improvement (P-score 0.896), as did pegozafermin 15 mg/week (P-score 0.956). Among approved agents, resmetirom 100 mg (RR 0.32; P-score 0.652) outranked semaglutide 2.4 mg (RR 0.54; P-score 0.373) for MASH resolution by indirect comparison, though confidence intervals overlapped; both were comparable for fibrosis improvement (P-scores 0.579 vs 0.507)."

Retrospective data • Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparative Efficacy and Safety of Incretin-Based Therapies, FGF21 Analogs, and Pan-PPAR Agonists for MASH: A Systematic Review and Bayesian Network Meta-Analysis (ACG 2026) - "Introduction: Metabolic dysfunctionâassociated steatohepatitis (MASH) is an increasing global health burden with limited approved therapies... A total of 14 RCT's comprising 8,462 patients were included, with 53.1% males and 46.9% females. Patients received semaglutide (n=1,642), tirzepatide (n=1,128), survodutide (n=612), retatrutide (n=318), efruxifermin (n=742), pegozafermin (n=512), lanifibranor (n=247), resmetirom (n=2,955), or placebo/standard therapy (n=306). Baseline age, BMI, diabetes prevalence, ALT, and fibrosis stages were comparable."

Retrospective data • Review • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Efruxifermin Induced a Rapid and Direct Antifibrotic Response That Was Sustained Through 96 Weeks in Phase 2b Trials of Participants With MASH and F2/3 Fibrosis or Cirrhosis (ACG 2026) - "Abstract text will be released on Sunday, October 11, 2026, at 12:00 pm CT (1:00 pm ET) when the ACG 2026 embargo lifts."

P2b data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

MASLD: Established Knowledge and Emerging Directions - Guideline Updates. (PubMed, Z Gastroenterol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major global health challenge, largely driven by the increasing prevalence of obesity and type 2 diabetes mellitus...Promising clinical data have been reported for resmetirom, semaglutide, tirzepatide, survodutide, lanifibranor, and fibroblast growth factor-21 analogues including efruxifermin, pegozafermin, and efimosfermin.This review summarises current and emerging diagnostic and therapeutic strategies and provides practical guidance for clinical management. In addition, a structured treatment algorithm for non-cirrhotic MASLD (F0-F3), restricted to therapies currently available in Europe and stratified according to diabetes status and fibrosis stage, is proposed as an evidence-based tool for routine clinical practice."

Journal • Review • Cardiovascular • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FGF21

A new era in the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD): clinical breakthroughs and challenges. (PubMed, Front Pharmacol) - "Metabolic dysfunction-associated steatotic liver disease (MASLD), affecting nearly one-third of adults worldwide, encompasses a spectrum from steatosis to steatohepatitis (MASH), advanced fibrosis, cirrhosis, and hepatocellular carcinoma, with fibrosis stage as the primary determinant of liver-related outcomes and cardiovascular disease as the leading cause of mortality. The period 2024-2026 has marked a transformative shift, with resmetirom (thyroid hormone receptor-β agonist) gaining accelerated approval in 2024 as the first agent to meet histologic endpoints in MASH, followed by semaglutide (GLP-1 receptor agonist) in 2025, both demonstrating substantial MASH resolution and fibrosis improvement in phase 3 trials; a diverse pipeline, including tirzepatide, efruxifermin, lanifibranor, denifanstat, and dual-incretin agonists, has yielded promising histologic and metabolic outcomes, with several advancing to phase 3 and updated guidelines endorsing pharmacotherapy for..."

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

From Recognition to Resolution: A Practical Framework for Diagnosing, Treating, and Managing MASH in the Liver/GI Specialty Setting (AASLD 2026) - "This program is designed for those who manage patients with MASH. CE: 1.5 CME HourFor more information and to register, visit: https://symposiareg.com/22614/ Objectives: Apply the AASLD-endorsed stepwise non-invasive testing framework including FIB-4, VCTE/ELF, and MRE to identify patients with MASH and significant fibrosis (F2F3) who are candidates for pharmacotherapy, and describe the role of liver biopsy in cases of diagnostic uncertainty Compare the mechanism of action, Phase 3 clinical evidence, patient selection criteria, and monitoring requirements for resmetirom and semaglutide 2.4 mg/week in patients with non-cirrhotic MASH and F2F3 fibrosis, and apply this comparison to individualized treatment decisions based on patient comorbidity profile Characterize the FGF21 analog class including efruxifermin and pegozafermin by mechanism of action, Phase 2 and Phase 3 evidence to date, and current regulatory status, and describe the evidence supporting the..."

Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Donor liver-derived FGF21 protects against tacrolimus-induced post-transplant diabetes mellitus through regulation of the CerS4/C18:0 ceramide lipotoxicity axis (TTS 2026) - "The long-acting FGF21-Fc fusion protein showed efficacy comparable to efruxifermin with reduced dosing frequency and improved 8-week survival in steatotic-graft LT rats...Figure 2. Effect of intraperitoneal injection of the long-acting FGF21-Fc fusion protein on glucose metabolism in LT rats receiving steatotic donor livers."

Post-transplantation • Diabetes • Metabolic Disorders • Transplantation • CERS4 • FGF21

Efficacy of efruxifermin in improving liver fibrosis in patients with metabolic dysfunction-associated steatohepatitis/nonalcoholic steatohepatitis: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Eur J Gastroenterol Hepatol) - "Subgroup analysis stratified by efruxifermin dosages showed that treatment with 28 mg dose (risk ratio = 1.71; 95% CI = 1.08-2.72; P = 0.02) and 50 mg dose (risk ratio = 1.75; 95% CI = 1.11-2.76; P = 0.02) showed significant improvement in fibrosis by greater than or equal to one stage without worsening of MASH. Among the various pharmacologic interventions, efruxifermin combines clinically meaningful antifibrotic efficacy with systemic metabolic improvements in a balanced profile."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Transplantation • FGF21

Differential therapeutic profile of the long-acting FGF21 analogue efruxifermin in the GAN DIO-MASH and CDAA-HFD mouse models of MASH (EASD 2026) - "EFX demonstrated a contrasting therapeutic profile in the two mouse models of MASH. In GAN DIO-MASH mice, EFX robustly improved metabolic and histological hallmarks of MASH while also improving quantitative fibrosis histology. Longer treatment durations may be required for EFX to reverse fibrosis stage in GAN DIO-MASH mice."

Preclinical • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • COL1A1 • FGF21 • TIMP1

A Study of Efruxifermin in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (Symmetry) (clinicaltrials.gov) - P2 | N=213 | Completed | Sponsor: Akero Therapeutics, Inc | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Aug 2025

Trial completion • Trial completion date • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

The Use of FGF21 Analogues in MASH and MASH Cirrhosis - Metabolic Master Regulators or Liver-Specific Mechanisms? (PubMed, JHEP Rep) - "In phase 2 clinical trials, efruxifermin, pegozafermin, and efimosfermin have demonstrated meaningful histological improvements in fibrotic MASH. FGF21 analogues appear particularly potent in inducing fibrosis regression even with modest weight loss, supporting a complementary combination strategy. Current evidence supports FGF21 pathway activation as a meaningful strategy to modify of MASH progression and potentially revert cirrhotic liver disesase."

Journal • Review • Diabetes • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • FGF21

AK-US-001-0105: A Study Evaluating Efruxifermin in Subjects With Non-Cirrhotic Nonalcoholic Steatohepatitis (NASH)/Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis (clinicaltrials.gov) - P3 | N=1650 | Recruiting | Sponsor: Akero Therapeutics, Inc | Trial completion date: Nov 2032 ➔ Feb 2033 | Trial primary completion date: Nov 2032 ➔ Feb 2033

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Efruxifermin Improved Liver Disease and Insulin Sensitivity in Participants with Type 2 Diabetes and Metabolic Dysfunction–Associated Steatohepatitis (MASH) Cirrhosis in the SYMMETRY Trial (ADA 2026) - P2 | "In this post hoc analysis, efruxifermin was associated with improvements in markers of liver disease and insulin sensitivity in individuals with T2D and MASH cirrhosis. Phase 3 trials of efruxifermin in MASH are ongoing."

Diabetes • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Study design, rationale, and baseline characteristics of the SYNCHRONY real-world trial: a phase 3 trial evaluating efruxifermin in participants non-invasively diagnosed with MASLD or MASH (EASL 2026) - P3 | "SYNCHRONY Real-World is one of three phase 3 trials evaluating the safety and efficacy of efruxifermin and includes participants representative of a broad spectrum of MASLD/MASH. Concurrent conduct of these trials allows for greater opportunities for participants to meet entry criteria. The results are expected in H1 2026."

Clinical • Non-invasive • P3 data • Real-world • Real-world evidence • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Hepatoprotective effects of Efruxifermin in the CDAA-HFD mouse model of advanced MASH with progressive fibrosis (EASL 2026) - "EFX improves biochemical and histological markers of fibrosis, but not steatosis or inflammation, in the non-obese CDAA-HFD mouse model of advanced MASH with progressive fibrosis."

Metastases • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • FGF21 • PTPRC

Efruxifermin ameliorates palmitate-induced hepatocyte lipotoxicity (EASL 2026) - "Agonism of FGF21's receptors on isolated heps reverses steatosis by directing FFA to mitochondria and increasing their oxidation. Despite increased oxidative flux, mtROS did not increase. This may have been the result of i) improved mitochondrial efficiency, ii) increased consumption of ATP (and regeneration of ADP) to support higher rates of gluconeogenesis, and/or iii) activation of adaptive stress response pathways."

Fibrosis • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • ACSL4 • FGF21

Efruxifermin improved digital pathology and noninvasive fibrosis measures in participants with MASH and advanced fibrosis or compensated cirrhosis: analysis of the HARMONY and SYMMETRY phase 2b trials (EASL 2026) - P2 | "In this post hoc analysis of participants with MASH at high risk of disease progression (F3 or F4c), efruxifermin was associated with improvements in continuous fibrosis measures assessed by digital pathology and noninvasive tests. Phase 3 trials of efruxifermin in MASH are ongoing."

Digital Pathology • Metastases • Non-invasive • P2b data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Liver Specific AAV Novel Capsid in Development of Long-termed Gene Therapy for MASH (ASGCT 2026) - "Recombinant FGF21 with extended half-life design such as Efruxifermin or Pegozafermin either with Fc or PEG modification, respectively, showed great efficacy in clinical trials for relatively high degree (F3-F4) of liver fibrosis in MASH. 2. The quantification of body weight and glucose up-take in MASH model study."

Gene therapy • Fibrosis • Gene Therapies • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Consistent efficacy of efruxifermin across PNPLA3 genotypes in phase 2b trials in MASH. (PubMed, Hepatology) - No abstract available

Journal • P2b data • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • PNPLA3

Fibroblast Growth Factor 21: Mechanisms, Therapeutic Potential, and Clinical Translation in Metabolic Dysfunction. (PubMed, Drug Des Devel Ther) - "In a Phase 2b trial, efruxifermin reversed cirrhosis in 39% of participants...This review aims to synthesize current evidence on the molecular mechanisms and therapeutic potential of FGF21 in metabolic dysfunction-associated steatohepatitis. It highlights emerging clinical data on FGF21 analogues and their role in targeting key pathways of disease progression, with implications for future therapeutic strategies."

Journal • Review • Cardiovascular • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21