Efruxifermin for NASH

Recruiting in Palo Alto (17 mi)

+181 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Akero Therapeutics, Inc

Disqualifiers: Alcoholic liver disease, Autoimmune disorders, Type 1 diabetes, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called efruxifermin (EFX) to see if it can help people with specific liver conditions. These conditions are hard to treat with current methods. EFX aims to improve liver health by reducing inflammation and fat buildup in the liver.

Do I need to stop my current medications for the Efruxifermin for NASH trial?

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 NASH?

Research shows that Efruxifermin, a drug designed to mimic a natural protein in the body, significantly reduced liver fat in patients with non-alcoholic steatohepatitis (NASH) during clinical trials. This suggests it may help improve liver health in people with this condition. ^{1 2 3 4 5}

How is the drug Efruxifermin unique for treating NASH?

Efruxifermin is unique because it is a fusion protein that combines a part of the human antibody with FGF21, a protein that helps regulate metabolism, and it specifically targets liver fibrosis in NASH, a condition with no approved treatments. Its mechanism involves binding to a specific receptor on cells to activate pathways that may reduce liver damage. ^{5 6 7 8 9}

Research Team

Eligibility Criteria

This trial is for adults aged 18-80 with a suspected or confirmed diagnosis of NASH/MASH or NAFLD/MASLD, and who have at least two components of metabolic syndrome or type 2 diabetes. It's not open to those with other liver diseases, type 1 diabetes, or unstable type 2 diabetes.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Efruxifermin or placebo for the assessment of safety and tolerability

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Efruxifermin (Growth Factor)

Trial Overview The study tests Efruxifermin (EFX) against a placebo in a controlled setting where neither the participants nor the researchers know who receives the actual drug. The goal is to see if EFX can help people with certain types of fatty liver disease.

Participant Groups

Group I: EFX 50 mg (Open-Label Rollover) Experimental Treatment 1 Intervention

Group II: EFX 50 mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Akero Therapeutics, Inc

Lead Sponsor

Trials

6

Recruited

3,900+

Findings from Research

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]

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 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]

Efruxifermin (EFX) is a promising treatment for liver fibrosis due to nonalcoholic steatohepatitis (NASH), showing a dose-proportional pharmacokinetic profile in a phase 2a study involving patients with moderate-to-advanced fibrosis or compensated cirrhosis.

A validated electrochemiluminescent immunoassay (ECLIA) was developed to accurately measure biologically active EFX in human serum, ensuring reliable pharmacokinetic assessments and demonstrating the importance of the intact C-terminus for EFX's pharmacological activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noncompetitive immunoassay optimized for pharmacokinetic assessments of biologically active efruxifermin. Kinne, AS., Tillman, EJ., Abdeen, SJ., et al.[2023]

The novel TNFR2 agonist NewSTAR2 shows improved serum retention and in vivo activity compared to the previously established STAR2, enhancing regulatory T cell (Treg) numbers by over 300% and maintaining elevated levels for up to 10 days after a single injection.

NewSTAR2 effectively protects against acute graft-versus-host disease (GvHD) when administered before allogeneic hematopoietic cell transplantation, demonstrating its potential as a powerful immunotherapy for autoinflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A TNFR2-Specific TNF Fusion Protein With Improved In Vivo Activity. Vargas, JG., Wagner, J., Shaikh, H., et al.[2022]

A new panel of highly specific monoclonal antibodies (mAbs) against human FcRn has been developed, which can help researchers study the expression and function of this important receptor in the body.

These mAbs can selectively block the binding of IgG antibodies and serum albumin to FcRn, providing a valuable tool for exploring therapeutic strategies that target FcRn to enhance drug delivery and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies directed against human FcRn and their applications. Christianson, GJ., Sun, VZ., Akilesh, S., et al.[2022]

Efgartigimod, an FcRn inhibitor, effectively reduced total IgG and autoreactive IgG levels in patients with pemphigus vulgaris and pemphigus foliaceus, showing early signs of improved disease activity and good tolerability during a phase 2 clinical trial.

Interestingly, while total IgG levels returned to baseline after treatment, autoreactive antibody levels remained low in some participants, suggesting a potential long-lasting immunomodulatory effect of efgartigimod beyond just blocking IgG recycling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus. Maho-Vaillant, M., Sips, M., Golinski, ML., et al.[2023]

A scaled-up pharmacokinetic model accurately predicted the effects of anti-FcRn monoclonal antibodies, like rozanolixizumab, on the levels of endogenous IgG in healthy human subjects, showing a maximum prediction error of only -8.50%.

The model suggests that anti-FcRn therapies may be more effective at lower doses in healthy individuals compared to patients with autoimmune diseases, indicating its potential for optimizing dosing strategies in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting the Effects of Anti-FcRn Therapy on the Disposition of Endogenous IgG in Humans. Li, T., Balthasar, JP.[2020]

References

1. 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]

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

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

3. 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]

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. England pubmed.ncbi.nlm.nih.gov

Noncompetitive immunoassay optimized for pharmacokinetic assessments of biologically active efruxifermin. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

A TNFR2-Specific TNF Fusion Protein With Improved In Vivo Activity. [2022]

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

Monoclonal antibodies directed against human FcRn and their applications. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

FcRn Antagonism Leads to a Decrease of Desmoglein-Specific B Cells: Secondary Analysis of a Phase 2 Study of Efgartigimod in Pemphigus Vulgaris and Pemphigus Foliaceus. [2023]

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

Development and Evaluation of a Physiologically Based Pharmacokinetic Model for Predicting the Effects of Anti-FcRn Therapy on the Disposition of Endogenous IgG in Humans. [2020]