Efruxifermin for Fatty Liver Disease

Recruiting at 256 trial locations

Overseen By Akero Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Akero Therapeutics, Inc

Disqualifiers: Other liver diseases, Type 1 diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

1150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called efruxifermin (EFX) for individuals with a type of liver disease known as NASH/MASH, which can lead to liver scarring (cirrhosis). The goal is to determine if EFX can improve liver function in those with compensated cirrhosis, where the liver is scarred but still functioning. Participants will receive either the treatment or a placebo (a harmless pill with no active medicine) to compare results. Individuals with confirmed cirrhosis due to NASH/MASH and no history of severe liver problems may be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

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.

Is there any evidence suggesting that efruxifermin is likely to be safe for humans?

Research has shown that efruxifermin (EFX) is generally safe and well-tolerated. In one study, patients taking EFX showed improved liver health, indicating that the treatment is effective and manageable for the body. Another review found that EFX did not cause serious side effects in patients with liver conditions such as NASH, a type of liver disease. These findings are encouraging for those considering participation in a clinical trial with EFX, as they suggest the medication is safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for fatty liver disease, which primarily focus on lifestyle changes and medications that address symptoms, Efruxifermin (EFX) offers a novel approach by acting as an engineered analog of fibroblast growth factor 21 (FGF21). This new mechanism targets liver health directly, aiming to reduce liver fat and improve liver function. Researchers are particularly excited because Efruxifermin has shown promise in significantly reducing liver fat content and improving fibrosis, potentially offering a more effective treatment option for patients with this condition.

What evidence suggests that efruxifermin might be an effective treatment for fatty liver disease?

Studies have shown that efruxifermin (EFX) may improve liver health in people with fatty liver disease, such as NASH or MASH. In earlier research, patients taking EFX demonstrated better results in reducing liver damage and scarring. One study found that EFX was safe and improved markers of liver damage. Another analysis found EFX to be well-tolerated and suggested it might help with scarring related to MASH. Overall, these findings suggest that EFX could effectively treat liver problems caused by fatty liver disease. Participants in this trial will receive either a 50 mg dose of EFX or a placebo to further evaluate its effectiveness and safety. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Efruxifermin

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

In a 12-week study involving 20 newly diagnosed overweight patients with type 2 diabetes and nonalcoholic fatty liver disease, liraglutide treatment led to a significant weight loss of 4.9 kg and a reduction in liver fat content.

Liraglutide also decreased plasma levels of fibroblast growth factor 21 (FGF21), suggesting that FGF21 could serve as a potential biomarker for assessing the effectiveness of liraglutide in improving liver fat and glucose metabolism.

NCBI (Pubmed)

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. Li, X., Wu, X., Jia, Y., et al.[2022]

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40818852/

Safety and efficacy of once-weekly efruxifermin versus ... Safety and efficacy of once-weekly efruxifermin versus placebo in metabolic dysfunction-associated steatohepatitis (HARMONY): 96-week results ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06161571

NCT06161571 | A Study Evaluating Efruxifermin in ... The aim of this study is to assess the safety and tolerability of EFX compared to placebo in subjects with non-invasively diagnosed NASH/MASH and NAFLD/MASLD.

3. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1594091/full

A systematic review and meta-analysis of efruxifermin's ... Efruxifermin may be a potential therapeutic for MASH-related fibrosis, with the available data indicating seemingly favorable tolerability.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36644237/

A randomized, double-blind, placebo-controlled phase IIa ... Conclusions: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379120300732

AKR-001, an Fc-FGF21 Analog, Showed Sustained ... Experimental fibroblast growth factor 21 (FGF21) analogs can improve lipid profiles in patients with metabolic diseases.

6. jcto.weill.cornell.edu jcto.weill.cornell.edu/open_clinical_trials/a-phase-3-randomized-double-blind-placebo-controlled-study-evaluating-the-safety-and-efficacy-of-efruxifermin-in-subjects-with-compensated-cirrhosis-due-to-nonalcoholic-steatohepatitis-nashmetabolic-dysfunction-associated

A Phase 3, Randomized, Double-Blind, Placebo ... The purpose of this research study is to evaluate the effect of the investigational study drug Efruxifermin (EFX) in treating compensated liver cirrhosis ...

7. wjgnet.com wjgnet.com/2150-5349/full/v16/i3/110709.htm

Safety and efficacy of efruxifermin in metabolic dysfunction- ... Safety and efficacy of efruxifermin in metabolic dysfunction-associated steatohepatitis: A systematic review.