Efimosfermin for Fatty Liver Disease

Recruiting at 35 trial locations

Overseen By Patricia Mendez, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boston Pharmaceuticals

Disqualifiers: Chronic liver disease, Type 1 diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21 weeks

42 Participants Needed

Trial Summary

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 Efimosfermin Alfa for treating fatty liver disease?

Research on a similar drug, efruxifermin, which is also a fibroblast growth factor 21 (FGF21) analog, showed it could reduce liver fat in patients with non-alcoholic steatohepatitis (NASH), a type of fatty liver disease. This suggests that Efimosfermin Alfa might also be effective in reducing liver fat in similar conditions. ^{1 2 3 4 5}

Is Efimosfermin safe for humans?

Efruxifermin, which is similar to Efimosfermin, has been tested for safety in patients with liver disease, and the trials focused on its safety and tolerability. While specific safety details for Efimosfermin are not provided, similar drugs have been evaluated for safety in clinical trials. ^{3 4 6 7 8}

How does the drug Efimosfermin Alfa differ from other treatments for fatty liver disease?

Efimosfermin Alfa is unique because it is a fibroblast growth factor 21 (FGF21) analog, which means it mimics a protein that helps reduce liver fat and improve liver health. This drug is administered through weekly subcutaneous injections, which is different from many other treatments that may be taken orally. ^{2 3 4 5 9}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety, tolerability, preliminary efficacy, and pharmacokinetics (PK) of efimosfermin in participants with metabolic dysfunction associated steatohepatitis (MASH) and compensated cirrhosis consistent with stage F4 fibrosis.

Eligibility Criteria

This trial is for adults aged 18-75 with compensated cirrhosis due to metabolic dysfunction associated steatohepatitis (MASH) and stage F4 fibrosis. Participants must have at least two components of metabolic syndrome and be able to give informed consent. Those with type 1 diabetes, other causes of chronic liver disease, or decompensated liver disease cannot join.

Inclusion Criteria

I have at least two symptoms of metabolic syndrome.

Other inclusion criteria may apply.

My liver biopsy shows stage F4 fibrosis.

Exclusion Criteria

I have a history of type 1 diabetes.

I have chronic liver disease but no history of severe liver failure.

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥5 × the upper limit of normal (ULN)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efimosfermin or placebo once every 4 weeks

21 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

79 weeks

Treatment Details

Interventions

• Efimosfermin Alfa

Trial Overview The study tests the safety and potential benefits of Efimosfermin Alfa in individuals with MASH-related cirrhosis. It compares this new treatment against a placebo while also studying how the body processes the drug.

Participant Groups

Group I: Efimosfermin (Dose 2) Experimental Treatment 1 Intervention

Participants will receive efimosfermin (Dose 2) Q4W.

Group II: Efimosfermin (Dose 1) Experimental Treatment 1 Intervention

Participants will receive efimosfermin (Dose 1) once every 4 weeks (Q4W).

Group III: Placebo Placebo Group 1 Intervention

Participants will receive placebo Q4W.

Who Is Running the Clinical Trial?

Boston Pharmaceuticals

Lead Sponsor

Trials

12

Recruited

910+

Findings from Research

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, 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]

Current treatments for nonalcoholic fatty liver disease (NAFLD) are still not very effective, but weight loss remains a key target for therapy despite being difficult to achieve.

Several investigational drugs show promise for treating NASH, but concerns about long-term safety exist, particularly with vitamin E and other medications like pioglitazone and obeticholic acid, which have notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for nonalcoholic steatohepatitis - a safety evaluation. Issa, D., Wattacheril, J., Sanyal, AJ.[2017]

In a meta-analysis of 41 randomized controlled trials involving 2,944 participants with non-alcoholic steatohepatitis (NASH), 68% of those on placebo experienced at least one adverse event (AE), highlighting the need for careful safety evaluations in this largely asymptomatic condition.

Serious adverse events were reported in 7.8% of placebo participants, with a notably higher incidence in phase 3 trials and those funded by pharmaceutical companies, indicating that the context of the study may influence safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo Adverse Events in Non-alcoholic Steatohepatitis Clinical Trials: A Pooled Analysis of 2,944 Participants. Tay, PWL., Ng, CH., Lin, SY., et al.[2023]

References

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

Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up. [2018]

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

Diagnostic and therapeutic implications of the association between ferritin level and severity of nonalcoholic fatty liver disease. [2021]

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

A randomized, double-blind, placebo-controlled trial of Aldafermin in patients with nonalcoholic steatohepatitis and compensated cirrhosis. [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

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

6. England pubmed.ncbi.nlm.nih.gov

Treatment options for nonalcoholic steatohepatitis - a safety evaluation. [2017]

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

Placebo Adverse Events in Non-alcoholic Steatohepatitis Clinical Trials: A Pooled Analysis of 2,944 Participants. [2023]

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

Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Independent Dose-Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease. [2021]