Efruxifermin for NASH

Recruiting at 233 trial locations

Overseen By Akero Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Akero Therapeutics, Inc

Disqualifiers: Cirrhosis, 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: 52 weeks

1650 Participants Needed

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 a specific liver condition called non-cirrhotic NASH/MASH. The patients have significant liver damage but not cirrhosis. EFX aims to improve liver health by reducing swelling and scarring in the liver.

Do I need to stop my current medications for the 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.

Is efruxifermin safe for humans?

Efruxifermin has been tested in several clinical trials for non-alcoholic steatohepatitis (NASH), and these studies primarily focused on its safety and tolerability. The trials generally found that efruxifermin was well-tolerated by patients, with no major safety concerns reported. ^{1 2 3 4 5}

What makes 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, which is necessary for its activity, making it different from other treatments that do not use this pathway. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Efruxifermin for NASH?

Research shows that Efruxifermin, a drug designed to treat non-alcoholic steatohepatitis (NASH), significantly reduced liver fat in patients during clinical trials. In a study, patients receiving Efruxifermin showed a notable decrease in liver fat compared to those who received a placebo, indicating its potential effectiveness for NASH. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for people with a liver condition called non-cirrhotic NASH or MASH, which involves fat buildup and fibrosis (scarring) at stage 2 or 3. Participants should not have cirrhosis, a more advanced liver scarring.

Inclusion Criteria

FibroScan® measurement > 7.5 kPa

I have NASH confirmed by a recent biopsy showing specific liver damage.

ELF score ≥ 7.7

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 under control.

My liver biopsy shows I have cirrhosis.

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 study

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

188 weeks

Long-term follow-up

Participants are monitored for event-free survival and other long-term outcomes

240 weeks

Treatment Details

Interventions

• Efruxifermin

Trial Overview The study tests Efruxifermin (EFX), comparing it to a placebo in a controlled setting. Participants are randomly assigned to either the drug group or the placebo group without knowing which one they receive.

Participant Groups

Group I: EFX 50 mg Experimental Treatment 1 Intervention

Group II: EFX 28 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 (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]

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 phase 2b study involving 171 patients with biopsy-confirmed NASH, aldafermin was generally well tolerated, with most adverse events being mild or moderate, indicating a favorable safety profile.

Although aldafermin did not show a significant improvement in liver fibrosis compared to placebo, it did demonstrate positive effects on several secondary endpoints, suggesting potential benefits that warrant further investigation in future NASH trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. Harrison, SA., Abdelmalek, MF., Neff, G., 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]

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 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]

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]

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. England pubmed.ncbi.nlm.nih.gov

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. Netherlands pubmed.ncbi.nlm.nih.gov

Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial. [2022]

7. 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]

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

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

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]

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

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