Pegozafermin
A long-acting FGF21 analogue given weekly or every two weeks, in phase 3 trials for fatty-liver hepatitis with scarring
Pegozafermin, first called BIO89-100, is a version of the hormone fibroblast growth factor 21 (FGF21) to which polyethylene glycol is attached at chosen sites using sugar-transferring enzymes, a process called glycoPEGylation. That stretches its half-life to about two to four days. In the phase 2b ENLIVEN trial in MASH with moderate or severe scarring, fibrosis improved in about a quarter of patients on the higher doses against 7% on placebo, and in severe hypertriglyceridaemia it roughly halved triglycerides in eight weeks. Phase 3 trials in MASH are running, now sponsored by Roche. It is not approved anywhere.
Used in human trials: 15 or 30 mg weekly, or 44 mg every two weeks, Weekly or every two weeks, Subcutaneous (Study: MASH with stage 2-3 fibrosis (ENLIVEN)) Details ↓
Recommended Dosing
Used in human trials
No manufacturer dose exists for this use: these are amounts given in published trials, not recommendations.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
FGF21 is a hormone made mainly by the liver that acts on liver, fat and other tissues through FGF receptors and the partner receptor β-Klotho, and natural FGF21 lasts only half an hour to two hours in the blood. Pegozafermin keeps the hormone's activity and adds polyethylene glycol at specific sites, attached with sugar-transferring enzymes, which slows its clearance to a half-life of 55 to 100 hours. In cell assays it engaged the same receptors as FGF21, with about eight times the potency at FGF receptor 1c. In diabetic monkeys weekly or fortnightly injections lowered triglycerides, cholesterol, glucose, HbA1c, liver enzymes, food intake and weight, and in healthy volunteers single doses improved triglycerides, cholesterol and adiponectin.
The phase 1b/2a study in 81 people with MASH or a high-risk metabolic profile tested 3 to 27 mg weekly and 18 or 36 mg every two weeks for 12 weeks. Liver fat on MRI fell by 9 to 15 percentage points more than placebo, liver enzymes and several lipids improved, and the most common related side effect was a mild increase in appetite without weight gain. Anti-drug antibodies appeared in 65% of treated participants. A 20-person open-label extension gave 27 mg weekly for 20 weeks to biopsy-confirmed MASH: liver fat fell by about 65%, 26% had fibrosis improvement and 32% had MASH resolution. Modelling of the exposure data pointed to 30 mg weekly or 44 mg every two weeks as near-maximal doses.
Those doses went into ENLIVEN, the phase 2b trial, with 15 mg weekly as a lower arm. Among 219 treated patients with stage 2 or 3 fibrosis, fibrosis improved by at least one stage without worsening MASH in 26% on 30 mg and 27% on 44 mg every two weeks, against 7% on placebo, and MASH resolved in 23% to 37% against 2%. Nausea and diarrhoea were the most frequent side effects. In a separate phase 2 trial in 85 people with severe hypertriglyceridaemia, eight weeks of treatment cut median triglycerides by 57% against 12% on placebo and lowered liver fat in an MRI substudy.
Phase 3 began in 2023 and 2024. ClinicalTrials.gov lists ENTRUST, in severe hypertriglyceridaemia, as completed in July 2025 with no results posted, and two MASH trials, one in stage 2 to 3 fibrosis and ENLIGHTEN-Cirrhosis in compensated cirrhosis, as recruiting under Hoffmann-La Roche. No phase 3 result has appeared in PubMed. This page stays at the mid tier because only seven PubMed abstracts that name pegozafermin could be read; secondary analyses of ENLIVEN whose titles do not name the drug are listed in the References. Until phase 3 reports and a regulator approves it, pegozafermin is available only in trials.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Mechanism of Action
Pegozafermin is a long-acting FGF21 that acts through the same FGF receptors and β-Klotho partner receptor.
FGF21 receptor activity
Same receptor profile as FGF21, about eightfold more potent at FGF receptor 1c (PMID 37562970).
GlycoPEGylation
Site-specific PEG extends the half-life to 55 to 100 hours (PMID 37562970).
Liver fat and lipids
Lowered liver fat and triglycerides in MASH and severe hypertriglyceridaemia (PMIDs 36521501, 37355760).
Published Research
Studies of pegozafermin (BIO89-100) read from their PubMed abstracts: the phase 1b/2a study and its biopsy extension, the population pharmacokinetic model, the ENLIVEN phase 2b trial, the phase 2 trial in severe hypertriglyceridaemia, the preclinical and healthy-volunteer study, and a review.
ENLIVEN: fibrosis in MASH
219 patients with biopsy-confirmed MASH and stage 2 or 3 fibrosis received 15 or 30 mg weekly, 44 mg every two weeks, or placebo for 24 weeks. Fibrosis improved without worse MASH in 22%, 26% and 27% against 7% (significant for the two higher doses), and MASH resolved in 37%, 23% and 26% against 2%. Nausea and diarrhoea were the main side effects.
Severe hypertriglyceridaemia
In a phase 2 trial of 85 patients with triglycerides of 500 to 2,000 mg/dL, eight weeks at four dose levels lowered median triglycerides by 57.3% pooled against 11.9% on placebo, with reductions of 36% to 63% across arms. Apolipoprotein B, non-HDL cholesterol and MRI liver fat (-42% against -8%) also fell, with no drug-related serious adverse events.
Phase 1b/2a: doses and safety
81 participants with MASH or a high-risk profile received 3, 9, 18 or 27 mg weekly, 18 or 36 mg every two weeks, or placebo for 12 weeks. Pharmacokinetics were dose-proportional, liver fat fell by 8.9 to 14.9 points more than placebo, and the most common related event was mild increased appetite. Anti-drug antibodies developed in 65% of those treated.
Biopsy extension at 27 mg
In an open-label cohort of 20 adults with MASH and stage 2 or 3 fibrosis given 27 mg weekly for 20 weeks, 63% met the main histology end point, 26% had fibrosis improvement and 32% MASH resolution, and MRI liver fat fell by about 65%. Side effects were mostly mild nausea and diarrhoea, with no serious events.
Choosing the phase 2b doses
Modelling the phase 1b/2a data, liver fat reduction tracked average drug levels whether doses were weekly or every two weeks. Simulations suggested 30 mg weekly gives close to the full effect and 44 mg every two weeks works like about 22 mg weekly, the basis for ENLIVEN's doses.
From cells and monkeys to volunteers
Pegozafermin matched FGF21's receptor profile with about eightfold higher potency at FGF receptor 1c. In diabetic monkeys it improved triglycerides, cholesterol, glucose, HbA1c, adiponectin, liver enzymes and weight; in healthy volunteers single doses improved lipids and adiponectin, with half-lives of 55 to 100 hours.
Review of its metabolic effects
This review describes pegozafermin as a glycopegylated FGF21 whose 55 to 100 hour half-life far exceeds natural FGF21's 0.5 to 2 hours, and summarises its effects on adiponectin, insulin sensitivity, triglyceride handling and fat production in the liver, along with the phase 2 hypertriglyceridaemia and MASH results.
Dosing Data
Pegozafermin is not approved, so there is no label. These are the doses given in the trials carded above.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the trials above.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
Pegozafermin is an investigational drug in phase 3; it has not been approved anywhere in the sources read.
Frequently Asked Questions
?What is pegozafermin?
A long-acting version of the hormone FGF21 with polyethylene glycol attached at chosen sites, injected weekly or every two weeks. It is being developed for MASH and was tested in severe hypertriglyceridaemia.
?Does it improve liver scarring?
In the phase 2b ENLIVEN trial, about a quarter of patients on 30 mg weekly or 44 mg every two weeks improved by one fibrosis stage in 24 weeks, against 7% on placebo. Phase 3 trials are testing whether that holds.
?Is it approved?
No. It is in phase 3 trials and available only within them.
?How does it differ from efruxifermin?
Both are long-acting FGF21 analogues. Efruxifermin is fused to an antibody Fc tail and given weekly; pegozafermin is glycoPEGylated and was tested weekly or every two weeks.
?What are the side effects?
Mostly mild nausea, diarrhoea and increased appetite in the trials. Many people developed antibodies to it in the early study.
References
- [registry] ClinicalTrials.gov API v2, read October 29, 2026: NCT06318169 (phase 3, MASH with fibrosis, recruiting) and NCT06419374 (phase 3, ENLIGHTEN-Cirrhosis, recruiting), sponsor Hoffmann-La Roche; NCT05852431 (ENTRUST, phase 3, severe hypertriglyceridaemia, completed July 7, 2025, no results posted); NCT04929483 (ENLIVEN, completed); NCT04541186 (phase 2 severe hypertriglyceridaemia, completed); NCT04048135 (phase 1b/2a, completed).
- [clinical-trial] Loomba R, et al. "Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH." N Engl J Med, 2023;389(11):998-1008. PMID: 37356033.
- [clinical-trial] Bhatt DL, et al. "The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial." Nat Med, 2023;29(7):1782-1792. PMID: 37355760.
- [clinical-trial] Loomba R, et al. "Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study." Lancet Gastroenterol Hepatol, 2023;8(2):120-132. PMID: 36521501.
- [clinical-trial] Alkhouri N, et al. "Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy-confirmed nonalcoholic steatohepatitis." Aliment Pharmacol Ther, 2023;58(10):1005-1015. PMID: 37718721.
- [clinical-trial] Tseng CL, et al. "Population Pharmacokinetics and Pharmacodynamics of Pegozafermin in Patients with Nonalcoholic Steatohepatitis." Clin Pharmacol Ther, 2023;114(6):1323-1331. PMID: 37696614.
- [pubmed] Rosenstock M, et al. "The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers." J Pharmacol Exp Ther, 2023;387(2):204-213. PMID: 37562970.
- [review] Bailey NN, et al. "Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review." Cardiol Rev, 2025;33(5):402-406. PMID: 37889055.
- [clinical-trial] Loomba R, et al. "Head-to-head comparison of MASH resolution index versus FAST for noninvasive prediction of resolution of MASH on biopsy." Hepatology, 2026;83(4):907-914. PMID: 40359098.
- [clinical-trial] Loomba R, et al. "Clinical Utility of a 50% and 30% Decline in Magnetic Resonance Imaging-Proton Density Fat Fraction in Predicting Fibrosis Improvement in Metabolic Dysfunction-Associated Steatohepatitis." Clin Gastroenterol Hepatol, 2026;24(10):2707-2714. PMID: 41655805.
- [pubmed] Loomba R, et al. "Clinical utility of a 30% reduction in VCTE-derived liver stiffness measurement for identifying histologic improvement in MASH." Hepatology, 2026;. PMID: 42691332.
- [review] Souza M, et al. "Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis." Hepatology, 2025;82(6):1523-1533. PMID: 39903735.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Trial status comes from ClinicalTrials.gov and approval status from Drugs@FDA (openFDA) and the EMA medicines list, read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.