Efruxifermin for Fatty Liver Disease

Recruiting at150 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Akero Therapeutics, Inc

Disqualifiers: Other liver diseases, Type 1 diabetes, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a multi-center evaluation of efruxifermin (EFX) in a randomized, double-blind, placebo-controlled study in subjects with compensated cirrhosis due to NASH/MASH.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that Efruxifermin, a drug similar to a natural protein in the body, significantly reduces liver fat in patients with non-alcoholic steatohepatitis (NASH), a type of fatty liver disease. In clinical trials, patients receiving Efruxifermin had a notable decrease in liver fat compared to those who received a placebo. ^{1 2 3 4 5}

Is efruxifermin safe for humans?

Efruxifermin has been tested in clinical trials for non-alcoholic steatohepatitis (NASH) and has shown to be generally safe and well-tolerated in humans, with studies focusing on its safety and tolerability in patients with different stages of liver fibrosis. ^{1 2 3 4 6}

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

Efruxifermin is unique because it is a long-acting fusion protein that mimics fibroblast growth factor 21 (FGF21), which helps regulate metabolism and protect cells. It is administered as a weekly subcutaneous injection and has shown significant reductions in liver fat content in clinical trials, making it a promising option for non-alcoholic steatohepatitis (NASH). ^{1 2 3 4 7}

Research Team

Eligibility Criteria

This trial is for individuals with compensated cirrhosis caused by non-alcoholic steatohepatitis (NASH) or metabolic-associated fatty liver disease (MAFLD). Specific eligibility details are not provided, but typically participants must meet certain health criteria and not have conditions that could interfere with the study.

Inclusion Criteria

I have cirrhosis from NASH/MASH confirmed by a biopsy or non-invasive methods.

I have cirrhosis from NASH/MASH confirmed by a biopsy.

Exclusion Criteria

I have a liver condition not caused by other known diseases.

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

I have had severe liver problems.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efruxifermin (EFX) or placebo in a randomized, double-blind, placebo-controlled manner

96 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term outcomes such as resolution of NASH/MASH and fibrosis improvement

5 years

Treatment Details

Interventions

• Efruxifermin (Growth Hormone Receptor Agonist)

Trial Overview The study is testing Efruxifermin (EFX), comparing it against a placebo in a controlled setting. Participants will be randomly assigned to either receive EFX or a placebo without knowing which one they're getting, to fairly measure the effects of the drug.

Participant Groups

Group I: EFX 50 mg Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Akero Therapeutics, Inc

Lead Sponsor

Trials

6

Recruited

3,900+

Findings from Research

In a phase 2b trial involving 128 patients with non-alcoholic steatohepatitis (NASH) and moderate to severe fibrosis, efruxifermin significantly improved liver fibrosis and resolved NASH in 39% of patients receiving 28 mg and 41% of those receiving 50 mg, compared to 20% in the placebo group.

Efruxifermin was generally well-tolerated, with most adverse events being mild to moderate, such as diarrhea and nausea, indicating its potential for further evaluation in larger phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. Harrison, SA., Frias, JP., Neff, G., et al.[2023]

Efruxifermin, an Fc-FGF21 fusion protein, was found to significantly reduce body weight gain in rats over both 4 and 26 weeks, even with increased food intake, indicating its potential efficacy in managing weight-related issues.

Unlike some other FGF21 analogues, efruxifermin decreased urine volume without affecting electrolyte balance, and it did not increase sympathetic activation, suggesting a favorable safety profile in terms of hormonal and blood pressure responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats. Tillman, EJ., Brock, WJ., Rolph, T.[2022]

Efruxifermin, a long-acting Fc-FGF21 fusion protein, significantly reduced hepatic fat fraction (HFF) in patients with non-alcoholic steatohepatitis (NASH) after 12 weeks of treatment, with reductions of -12.3%, -13.4%, and -14.1% for the 28 mg, 50 mg, and 70 mg doses, respectively, compared to a negligible change of 0.3% in the placebo group.

The treatment was generally well-tolerated, with 89% of patients experiencing at least one treatment-emergent adverse event, mostly mild to moderate gastrointestinal issues, indicating an acceptable safety profile for efruxifermin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. Harrison, SA., Ruane, PJ., Freilich, BL., et al.[2023]

Efruxifermin was found to be safe and well-tolerated in a study of 30 patients with compensated NASH cirrhosis, with most adverse events being mild to moderate gastrointestinal issues.

After 16 weeks of treatment, efruxifermin showed significant improvements in liver injury markers and fibrosis, with 33% of patients experiencing fibrosis improvement and 25% achieving resolution of NASH, compared to none in the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. Harrison, SA., Ruane, PJ., Freilich, B., et al.[2023]

In a study using mice with nonalcoholic fatty liver disease (NAFLD), the expression of Amphiregulin (AREG) increased alongside proinflammatory cytokines, indicating its role in promoting liver inflammation during disease progression.

AREG was found to enhance the production of inflammatory mediators like IL-6 and IL-1β in liver cells, activating key signaling pathways (NF-κB and MAPKs) that lead to increased expression of iNOS and COX-2, which are associated with inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amphiregulin Induces iNOS and COX-2 Expression through NF-κB and MAPK Signaling in Hepatic Inflammation. Heo, YJ., Lee, N., Choi, SE., et al.[2023]

Altenusin (2076A), a natural FXR agonist, significantly reduced body weight and fat mass in mice on a high-fat diet, demonstrating its potential as a treatment for nonalcoholic fatty liver disease (NAFLD).

The treatment with 2076A improved blood glucose and insulin levels, and reversed liver fat accumulation, indicating its mechanism may involve enhanced insulin sensitivity and reduced liver fat production, with effects confirmed in FXR knockout mice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty Liver Disease by Activating the Farnesoid X Receptor. Zheng, Z., Zhao, Z., Li, S., et al.[2022]

References

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

Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial. [2023]

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

Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats. [2022]

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

Efruxifermin in non-alcoholic steatohepatitis: a randomized, double-blind, placebo-controlled, phase 2a trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase IIa trial of efruxifermin for patients with compensated NASH cirrhosis. [2023]

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

Amphiregulin Induces iNOS and COX-2 Expression through NF-κB and MAPK Signaling in Hepatic Inflammation. [2023]

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

Altenusin, a Nonsteroidal Microbial Metabolite, Attenuates Nonalcoholic Fatty Liver Disease by Activating the Farnesoid X Receptor. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Liraglutide Decreases Liver Fat Content and Serum Fibroblast Growth Factor 21 Levels in Newly Diagnosed Overweight Patients with Type 2 Diabetes and Nonalcoholic Fatty Liver Disease. [2022]