Pegozafermin for Fatty Liver Disease

Recruiting at145 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: 89bio, Inc.

Disqualifiers: Chronic liver diseases, Cirrhosis, Diabetes, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The study will assess the efficacy and safety of 2 dose regimens of pegozafermin for the treatment of liver fibrosis stage 2 or 3 in adult participants with MASH (previously known as nonalcoholic steatohepatitis \[NASH\]).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking vitamin E at more than 400 IU per day, you must have been on a stable dose for at least 6 months before the screening.

What data supports the effectiveness of the drug Pegozafermin for treating fatty liver disease?

Research shows that Pegozafermin, a drug similar to a natural hormone called FGF21, has improved liver health and metabolism in both diabetic monkeys and healthy humans. In a study with patients having severe high triglycerides, Pegozafermin significantly reduced liver fat and triglyceride levels, suggesting it could be effective for fatty liver disease. ^{1 2 3 4 5}

Is Pegozafermin safe for humans?

Pegozafermin has been studied in humans and showed improvements in metabolic markers without major safety concerns in trials for nonalcoholic steatohepatitis and severe hypertriglyceridemia. It was tested in both healthy volunteers and patients with these conditions, and no significant safety issues were reported. ^{1 2 3 5 6}

How is the drug Pegozafermin unique for treating fatty liver disease?

Pegozafermin is unique because it is a long-acting version of a hormone called FGF21, which helps regulate energy and fat in the body. It is given as a shot under the skin and has shown promising results in improving liver health and metabolism in early studies. ^{2 3 4 5 6}

Research Team

Millie Gottwald, PharmD

Principal Investigator

89bio, Inc.

Eligibility Criteria

Adults aged 18-75 with a BMI of ≥25 (≥23 for Asians) and <50, diagnosed with MASH (formerly NASH) having moderate to severe liver fibrosis are eligible. They must have had a recent biopsy confirming the disease stage and severity. Pregnant individuals or those outside the BMI range are excluded.

Inclusion Criteria

My liver biopsy shows I have moderate to severe fatty liver with inflammation and damage.

I am between 18 and 75 years old and not pregnant.

Body mass index (BMI) at screening ≥25.0 (≥23 for Asian participants) and <50.0 kg/m^2

Exclusion Criteria

I have type 1 diabetes or my type 2 diabetes is not well-controlled.

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥250 U/L

I have been taking the same dose of vitamin E (>400 IU/day) for at least 6 months.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pegozafermin or placebo for the treatment of liver fibrosis stage 2 or 3 in adult participants with MASH

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pegozafermin (Growth Factor)

Trial Overview The trial is testing two different doses of Pegozafermin against a placebo to see if they're effective and safe in treating stages 2 or 3 liver fibrosis in adults with MASH. Participants will be randomly assigned to receive either the drug or placebo.

Participant Groups

Group I: Pegozafermin Regimen 2 Experimental Treatment 1 Intervention

Group II: Pegozafermin Regimen 1 Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Matched Placebo will be administered in Regimens 1 and 2.

Who Is Running the Clinical Trial?

89bio, Inc.

Lead Sponsor

Trials

7

Recruited

2,600+

Findings from Research

In a phase 1b/2a study involving 81 participants with non-alcoholic steatohepatitis (NASH), pegozafermin was found to be generally well tolerated and led to significant reductions in liver fat and improvements in liver function markers compared to placebo.

Pegozafermin also showed beneficial effects on lipid profiles, with notable reductions in triglycerides and LDL cholesterol, indicating its potential as a therapeutic option for managing NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Loomba, R., Lawitz, EJ., Frias, JP., et al.[2023]

In a phase 2a study involving 75 patients with non-alcoholic steatohepatitis, pegbelfermin significantly reduced hepatic fat fraction after 16 weeks of treatment, with a decrease of -6.8% for the daily dose and -5.2% for the weekly dose compared to placebo.

The treatment was generally well tolerated, with most adverse events being mild, indicating a favorable safety profile for pegbelfermin in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. Sanyal, A., Charles, ED., Neuschwander-Tetri, BA., et al.[2019]

Pegozafermin, a modified version of FGF21, shows significantly higher potency in engaging its receptor and has demonstrated rapid improvements in metabolic biomarkers like triglycerides and cholesterol in diabetic monkeys with weekly or bi-weekly dosing.

In healthy volunteers, pegozafermin led to significant reductions in triglycerides and improvements in cholesterol levels, with a long half-life of 55 to 100 hours, indicating its potential as a long-acting treatment for nonalcoholic steatohepatitis and severe hypertriglyceridemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers. Rosenstock, M., Tseng, L., Pierce, A., et al.[2023]

In a phase 2 trial involving 67 patients with severe hypertriglyceridemia, pegozafermin significantly reduced triglyceride levels by 57.3% compared to 11.9% in the placebo group, meeting the primary endpoint of the study.

Pegozafermin also led to significant decreases in apolipoprotein B and non-high-density lipoprotein cholesterol, as well as a reduction in liver fat, with no serious adverse events related to the drug, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial. Bhatt, DL., Bays, HE., Miller, M., et al.[2023]

In a 12-week study involving 120 patients with obesity and type 2 diabetes, pegbelfermin did not significantly lower HbA1c levels, indicating it may not directly affect blood sugar control.

However, the 20 mg daily dose of pegbelfermin improved cholesterol and triglyceride levels, and increased adiponectin, suggesting potential benefits for metabolic health and liver fibrosis in patients predisposed to fatty liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study. Charles, ED., Neuschwander-Tetri, BA., Pablo Frias, J., et al.[2020]

In a phase 2b trial involving 222 patients with biopsy-proven noncirrhotic NASH, pegozafermin significantly improved fibrosis, with 26% of patients in the 30 mg group showing improvement compared to only 7% in the placebo group.

Pegozafermin also demonstrated a notable effect on NASH resolution, with 37% of patients in the 15 mg group achieving resolution compared to just 2% in the placebo group, indicating its potential as an effective treatment for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. Loomba, R., Sanyal, AJ., Kowdley, KV., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), a PEGylated fibroblast growth factor 21 analogue, in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 2a trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

The Novel GlycoPEGylated FGF21 Analog Pegozafermin Activates Human FGF Receptors and Improves Metabolic and Liver Outcomes in Diabetic Monkeys and Healthy Human Volunteers. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Pegbelfermin (BMS-986036), PEGylated FGF21, in Patients with Obesity and Type 2 Diabetes: Results from a Randomized Phase 2 Study. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH. [2023]