pegozafermin (BIO89-100) / 89Bio - LARVOL DELTA

TRIGLYCERIDE REDUCTION WITH PEGOZAFERMIN IS HIGHLY CORRELATED ACROSS METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS AND SEVERE HYPERTRIGLYERIDEMIA - Kevin Maki (ACC 2025) - No abstract available

Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

89bio Provides Business Update and Outlook for 2025 (GlobeNewswire) - "Completed enrollment in ENTRUST, the Phase 3 trial evaluating the efficacy, safety and tolerability of pegozafermin in patients with SHTG. 89bio expects to report topline 26-week data from this trial in the second half of 2025."

P3 data: top line • Severe Hypertriglyceridemia

Efruxifermin Harmony 96 Weeks/Pegozafermin 48 Week (MASH-TAG 2025) - No abstract available

89bio, Inc. Announces Proposed Underwritten Public Offering of Common Stock and Pre-Funded Warrants (GlobeNewswire) - "89bio, Inc...today announced that it has commenced an underwritten public offering of $100 million of shares of its common stock or, in lieu of common stock to certain investors that so choose, pre-funded warrants to purchase shares of its common stock. In addition, 89bio is expected to grant the underwriters of the offering an option for a period of 30 days to purchase up to an additional $15 million of shares of its common stock at the public offering price, less the underwriting discounts and commissions....89bio intends to use the net proceeds from this proposed offering to fund ongoing clinical activities and development of pegozafermin, manufacturing related costs and other general corporate purposes, including working capital and operating expenses."

Financing • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

89bio Presents New Analyses Evaluating Pegozafermin and Potential Benefit of Non-Invasive Tests from the ENLIVEN Phase 2b Trial in MASH Patients at AASLD The Liver Meeting 2024 (GlobeNewswire) - "89bio, Inc...announced new analyses of data from the Phase 2b ENLIVEN trial evaluating pegozafermin in metabolic dysfunction-associated steatohepatitis (MASH) patients with advanced fibrosis. The findings were presented in four poster sessions at The American Association for the Study of Liver Diseases (AASLD) The Liver Meeting being held in San Diego, California."

P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Safety and Efficacy of Pegozafermin for Treatment of MASH and Hypertriglyceridemia: A Meta-Analysis (ACG 2024) - "247 patients in 3 RCTs were included in the study. The results showed that Pegozafermin increased adiponectin levels and decreased ALT levels, serum triglyceride levels. Moreover, it also showed that the Pegozafermin group had decreased liver volume (Combined effect: -208.96 ml, p < 0.0001) and decreased liver fat content (-8.36%) as compared to the placebo as shown in figure 1."

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

Fibroblast Growth Factor Analogues in Metabolic Dysfunction Associated Steatotic Liver Disease: A Network Meta-Analysis (ACG 2024) - "Twelve RCTs comprising 1,420 patients with MASLD were included, involving four FGF agonists: efruxifermin, aldafermin, pegbelfermin, and pegozafermin at various doses. Most significant mean reduction in hepatic fat fraction (HFF) [MD = -67.98, 95% CI [-102.12; -33.84], P 30% [RR=4.68, 95% CI [2.57; 7.97], P1 stage without MASH worsening followed by efruxifermin at 50 mg ( P =0.04)."

Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Novel Coronavirus Disease • FGF

MASH 2B TRIALS- A SYSTEMATIC REVIEW (AASLD 2024) - "These include PPAR agonists, SGLT-2 inhibitors, GLP-1 inhibitors, and the recently approved Resmetirom...The Harmony trial with efruxifermin showed significant fibrosis improvement, while the Enliven trial with pegozafermin also demonstrated significant fibrosis reduction at higher doses...Alpine 2/3 and Alpine 4 trials with aldafermin showed mixed results, with significant fibrosis improvement only in specific doses. The TANDEM trial, comparing Tropifexor and Cenicriviroc, focused on safety and efficacy, showing ALT, AST, and GGT reductions... RCTs in NASH treatment showed mixed outcomes. Lanifibranor and icosabutate showed promise, especially in T2D patients. FGF21 analogues like efruxifermin improved fibrosis, while FGF19 trials had variable results."

Review • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • Pain • Solid Tumor • Type 2 Diabetes Mellitus • FGF19 • FGF21

COMPARATIVE EFFICACY OF PHARMACOLOGIC THERAPIES FOR MASH IN REDUCING LIVER FAT CONTENT: SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (AASLD 2024) - "By comparison of absolute MRI-PDFF decline at 24 weeks, aldafermin (SUCRA: 83.65), pegozafermin (SUCRA: 83.46), and pioglitazone (SUCRA: 71.67) were the most efficacious interventions. Efinopegdutide (SUCRA: 67.02), semaglutide + firsocostat (SUCRA: 62.43), and pegbelfermin (SUCRA: 61.68) were the most efficacious interventions for achieving ≥30% decline in MRI-PDFF at 24 weeks...Efruxifermin, aldafermin and pegozafermin were the most efficacious for MRI-PDFF decline at 12 weeks by both the absolute decline and achieving ≥30% decline in MRI-PDFF. At 48 weeks, Cilofexor + firsocostat, selonternib + firsocostat and cilofexor were most efficacious in absolute reduction in MRI-PDFF, while semglutide, tropifexor and tropifexor + cenicriviroc were most efficacious in achieving ≥30% decline in MRI-PDFF... This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat as assessed by MRI-PDFF. These data may help inform the design and..."

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

DIAGNOSTIC POTENTIAL OF FAST AND AGILE3+ SCORES FOR F2/F3 FIBROSIS: AN ANALYSIS OF THE PHASE 2 ENLIVEN STUDY (AASLD 2024) - " ENLIVEN was a Phase 2, double-blind, placebo-controlled, 48-week study of pegozafermin (FGF-21 analog) in patients with biopsy-proven MASH with fibrosis (F2/F3)... FAST and AGILE3+ performed reasonably well in identifying their target populations in ENLIVEN. Because AGILE3+ was designed to identify F3+ patients, it was less accurate in identifying the overall F2/F3 population. These data suggest the FAST score would likely be a viable tool to reduce screen failures in clinical trials targeting F2/F3 fibrosis and/or to aid in treatment-making decisions, in the real-world setting."

P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

QUANTITATIVE ANALYSIS AND INTEGRATION OF MACHINE LEARNING FOR BIOMARKER ASSESSMENTS AND THEIR ASSOCIATION WITH TREATMENT RESPONSE: INSIGHTS FROM THE ENLIVEN PHASE 2B TRIAL OF PEGOZAFERMIN (AASLD 2024) - "Pegozafermin treatment led to improvements in multiple biomarkers which correlated to histological endpoints. The cluster analysis identified three distinct groups which remained consistent across both unsupervised and supervised ML approaches. Longer treatment duration (>24 weeks) can have different or better histological treatment effect; the relationship associated with the identified biomarkers shall be further explored."

Biomarker • Machine learning • P2b data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

PEGOZAFERMIN REDUCED PROGRESSION TO CIRRHOSIS: A POST-HOC ANALYSIS FROM THE PHASE 2B ENLIVEN STUDY (AASLD 2024) - "Treatment with PGZ led to a reduction in the proportion of subjects with BL fibrosis stage F3 who progressed to cirrhosis. Relative to PBO F3 progressors, PGZ-treated progressors demonstrated improvement in histological disease activity and multiple liver-related NITs, indicating that PGZ may have clinical benefits even in patients with histological fibrosis progression. PGZ is currently being studied in Phase 3 studies in non-cirrhotic and cirrhotic MASH."

P2b data • Retrospective data • Cardiovascular • Fibrosis • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • FGF21 • PRO-C3

BIOMARKER RESPONSE IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (MASH) PATIENTS WITH HIGH-RISK BASELINE FAST SCORES: OBSERVATIONS FROM THE ENLIVEN PHASE2B TRIAL WITH PEGOZAFERMIN (AASLD 2024) - "PGZ treatment in patients with a high FAST score at baseline shifted the majority to low-risk and was associated with benefit across various NITs over 48 weeks. These data suggest PGZ can be highly efficacious in non-cirrhotic patients with the greatest need for treatment."

Biomarker • Clinical • P2b data • Cardiovascular • Diabetes • Hepatology • Hypertension • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus • FGF21

"Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH" (AASLD 2024) - No abstract available

Clinical • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

89bio to Present New Analyses from ENLIVEN Phase 2b Pegozafermin Trial in Metabolic Dysfunction-Associated Steatohepatitis (MASH) at AASLD The Liver Meeting 2024 (GlobeNewswire) - "89bio, Inc...today announced that new analyses of data from the Phase 2b ENLIVEN trial evaluating pegozafermin in patients with metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis will be featured in four poster presentations at the upcoming 75th Annual American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2024 being held November 15 to 19, 2024 in San Diego, California."

P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

89bio Reports Second Quarter 2024 Financial Results and Corporate Updates (GlobeNewswire) - "Severe Hypertriglyceridemia (SHTG): Enrollment is ongoing in ENTRUST, the Phase 3 trial evaluating the efficacy, safety and tolerability of pegozafermin in patients with SHTG. Topline results from this trial are expected to be reported in 2025."

Enrollment status • P3 data: top line • Hypertriglyceridemia • Severe Hypertriglyceridemia

89bio Reports Second Quarter 2024 Financial Results and Corporate Updates (89bio) - "ENLIGHTEN-Cirrhosis...was initiated in the second quarter....The trial will enroll approximately 760 patients, who will be randomized in a 1:1 ratio to either receive 30mg of pegozafermin administered weekly or a placebo. A subset of the 760 patients will be evaluated at 24 months to assess fibrosis regression, potentially supporting an accelerated approval filing in the United States and conditional approval in Europe. The primary endpoint of fibrosis regression is defined as an improvement in fibrosis from F4 to an earlier stage. The primary endpoint for the final analysis will be a clinical outcome composite and is expected to form the basis for confirmatory or full approval. Data from the ENLIVEN Phase 2b trial was presented at the European Association for the Study of the Liver Congress (EASL) and was selected for the Poster Tour, a dedicated discussion session."

New P3 trial • P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparative efficacy of pharmacologic therapies for MASH in reducing liver fat content: Systematic review and network meta-analysis. (PubMed, Hepatology) - "This study provides an updated, relative rank-order efficacy of therapies for MASH in reducing hepatic fat. These data may help inform the design and sample size calculation of future clinical trials and assist selection of combination therapy."

Journal • Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Pegozafermin added to background GLP-1 therapy in patients with metabolic dysfunction-associated steatohepatitis with F2/F3 fibrosis: ENLIVEN 48-week extension data (EASL-ILC 2024) - "Most received semaglutide (53%) or dulaglutide (36%) along with additional T2DM medications. In MASH patients with F2/F3 fibrosis who were receiving background GLP-1 therapy, addition of PGZ demonstrated additional and sustained improvement in markers of liver and metabolic health compared to GLP-1 therapy alone. Confirmatory phase 3 studies are planned to begin in 2024 and will include patients on background incretin therapies per local standard of care."

Clinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • Type 2 Diabetes Mellitus • FGF21 • PRO-C3

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

Study Design of a Phase 3 Randomized Controlled Trial Evaluating the Efficacy and Safety of Pegozafermin in Patients with Severe Hypertriglyceridemia (NLA 2024) - P3 | "ENTRUST is a pivotal Phase 3 clinical trial designed to confirm the efficacy and safety of PGZ in the treatment of SHTG. Expected clinical benefits include significant reductions of triglycerides and hepatic steatosis, as well as other metabolic improvements."

Clinical • P3 data • Cardiovascular • Dyslipidemia • Gastroenterology • Hepatology • Hypertension • Hypertriglyceridemia • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • FGF21

Week 48 results from the phase 2b ENLIVEN extension study investigating pegozafermin for the treatment of metabolic dysfunction-associated steatohepatitis with fibrosis (EASL-ILC 2024) - "These robust results substantiate the sustained efficacy of PGZ treatment up to 48 weeks on NITs and metabolic markers in MASH patients with advanced fibrosis. PGZ continues to demonstrate a favorable safety and tolerability profile. Confirmatory phase 3 studies are planned for 2024."

P2b data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Efficacy and safety of FGF21 analogues in the treatment of metabolic dysfunction-associated steatohepatitis: an updated systematic review and meta-analysis (EASL-ILC 2024) - "Among them, 3 studies used Efruxifermin (238 patients), 3 used Pegbelfermin (426 patients) and 1 used Pegozafermin (222 patients). FGF21 analogues seem effective and safe in obese patients with biopsy-confirmed MASH, but the clinical benefit may be restricted to non-cirrhotic patients. New RCTs are necessary establish FGF21 analogues as a therapy for MASH."

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

Prediction of metabolic dysfunction-associated steatohepatitis resolution (EASL-ILC 2024) - " This prospective study included 163 participants (64% female) with biopsy-proven MASH and stage 2 or stage 3 fibrosis from a randomized, multicenter, placebo-controlled trial of pegozafermin, a fibroblast growth factor 21 analog... The MASH Resolution Index has superior diagnostic accuracy for MASH Resolution, compared to the FAST score."

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