pegozafermin (RG6881) / 89Bio, Roche - LARVOL DELTA

A Study to Assess the Effect of Subcutaneous Injection Site on the Pharmacokinetics of Pegozafermin in Healthy Participants (clinicaltrials.gov) - P1 | N=105 | Not yet recruiting | Sponsor: Hoffmann-La Roche

New P1 trial

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

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

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

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

Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH. (PubMed, Hepatology) - "A ≥30% relative decline in LSM by VCTE had modest accuracy to detect fibrosis regression without worsening MASH. More effective biomarkers for treatment response are required."

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

Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH (clinicaltrials.gov) - P3 | N=762 | Not yet recruiting | Sponsor: 89bio, Inc.

New P3 trial • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis) (clinicaltrials.gov) - P3 | N=1050 | Not yet recruiting | Sponsor: 89bio, Inc.

New P3 trial • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis) (clinicaltrials.gov) - P3 | N=1050 | Recruiting | Sponsor: 89bio, Inc. | Trial primary completion date: Dec 2026 ➔ Feb 2029

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

A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis) (clinicaltrials.gov) - P3 | N=1050 | Recruiting | Sponsor: 89bio, Inc. | Not yet recruiting ➔ Recruiting

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

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

Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH (clinicaltrials.gov) - P3 | N=762 | Recruiting | Sponsor: 89bio, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH (clinicaltrials.gov) - P3 | N=762 | Recruiting | Sponsor: 89bio, Inc. | Trial primary completion date: Apr 2030 ➔ Jun 2028

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

Pegozafermin: Regulatory submissions in US/EU for F2 or F3 MASH in 2028 (Roche) - Roche Group Development Pipeline: Regulatory submissions in US/EU for F4 MASH in 2028

EMA filing • FDA filing • Metabolic Dysfunction-Associated Steatohepatitis

ENTRUST: To Evaluate the Efficacy and Safety of Pegozafermin in Subjects With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=369 | Completed | Sponsor: 89bio, Inc. | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia • APOB

Use of the ANTICIPATE NASH risk score to stratify patients with compensated MASH cirrhosis: data from a phase 3, double-blinded, randomized clinical trial assessing the safety and efficacy of pegozafermin (ENLIGHTEN-cirrhosis) (EASL 2026) - P3 | "Higher AN categories were associated with greater severity across multiple, complementary assessments of cirrhosis (NITs, biopsy findings, presence of varices) in this large cohort of well-characterized subjects with MASH-cirrhosis. These findings support the utility of AN for stratifying patients across the compensated MASH-cirrhosis spectrum."

Clinical • P3 data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

Patients with compensated MASH cirrhosis and Fibroscan® VCTE score <15 kPa: baseline data from a phase 3, double-blinded, randomized clinical trial assessing the safety and efficacy of pegozafermin (ENLIGHTEN-Cirrhosis) (EASL 2026) - P3 | "Cirrhosis would have been missed in >1/3 of randomized subjects in this large cohort of well- characterized subjects with biopsy-proven MASH-cirrhosis if a VCTE score <15 kPa been used to exclude cirrhosis. Although data from a clinical trial may not be fully representative of patients with MASH cirrhosis in general, they suggest that exclusion of cirrhosis by a VCTE-LSM score ≤15 kPa cut-off may lead to inadvertent initiation of drugs for non-cirrhotic MASH and failure to initiate indicated standard-of-care management in a substantial proportion of patients with MASH cirrhosis."

Clinical • P3 data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Use of the ANTICIPATE NASH risk score to stratify patients with compensated MASH cirrhosis: data from a phase 3, double-blinded, randomized clinical trial assessing the safety and efficacy of pegozafermin (ENLIGHTEN-cirrhosis) (EASL 2026) - No abstract available

Clinical • P3 data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Triglyceride-lowering therapies for hepatic steatosis: mechanisms, efficacy, and clinical perspectives. (PubMed, Front Pharmacol) - "This review explores current and emerging TG-lowering therapies, including fibrates, omega-3 fatty acids, pemafibrate, and novel agents such as pegozafermin (an FGF21 analog), and APOC3 and angiopoietin-like protein 3 (ANGPTL3) inhibitors, in the context of hepatic steatosis and MASLD. While several agents demonstrate promise in reducing intrahepatic fat deposition and improving liver-related outcomes, further large-scale studies are required to establish their long-term efficacy and safety, and potential for disease modification in MASLD/metabolic dysfunction-associated steatohepatitis (MASH). Triglyceride-targeted therapies may offer a valuable adjunct or complementary approach to current treatment paradigms focused on weight loss, insulin sensitization, and antagonizing inflammation."

Journal • Review • Dyslipidemia • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • ANGPTL3 • FGF21

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

Current and Emerging Pharmacological Therapies for Hypertriglyceridemia. (PubMed, Int J Mol Sci) - "Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • ANGPTL3 • FGF21 • LPL

Comparative efficacy of pharmacologic therapies for MASLD in improving fibrosis: systematic review and network meta-analysis. (PubMed, Eur J Gastroenterol Hepatol) - "For the primary outcome, pegozafermin, obeticholic acid (OCA), and resmetirom all outperformed placebo in the fibrosis stage F1-3 analysis. Several new drugs currently in clinical trials have shown potential therapeutic effects for fibrosis improvement in MASLD patients, especially those targeting fibroblast growth factor 21 (FGF21). More definitive efficacy will depend on the results of phase III clinical trials."

Clinical • Journal • Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

BIO89-100-131: A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-fibrosis) (clinicaltrialsregister.eu) - P2/3 | N=260 | Recruiting | Sponsor: 89bio Inc.

New P2/3 trial • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Clinical utility of a 50% and 30% decline in MRI-PDFF in predicting fibrosis improvement in metabolic dysfunction-associated steatohepatitis. (PubMed, Clin Gastroenterol Hepatol) - "MRI-PDFF super-response predicts fibrosis regression without worsening MASH, and a greater likelihood of MASH resolution without worsening fibrosis than MRI-PDFF response."

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

Efficacy and safety of fibroblast growth factor 21 analogs in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: A systematic review and network meta-analysis. (PubMed, J Pharmacol Exp Ther) - "Among them, 284 received efruxifermin, 263 received pegbelfermin, 151 received pegozafermin, 65 received efimosfermin, 139 received MK-3655, and 375 received a placebo. SIGNIFICANCE STATEMENT: This meta-analysis evaluates the efficacy of fibroblast growth factor 21 analogs in improving metabolic dysfunction-associated steatotic liver disease. Efruxifermin and pegozafermin were the most significant in improving liver fibrosis; moreover; significant improvements in some metabolic parameters were observed with efimosfermin α, efruxifermin, and pegozafermin."

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