Efimosfermin for Fatty Liver Disease

Recruiting at 36 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests efimosfermin, a new treatment for people with fatty liver disease, specifically metabolic dysfunction-associated steatohepatitis (MASH) with liver scarring. The trial aims to assess the safety, tolerability, and effectiveness of the treatment in this condition. Participants will receive either one of two doses of efimosfermin or a placebo for comparison. This trial suits those diagnosed with MASH and liver scarring, along with at least two signs of metabolic syndrome, such as high blood pressure or high blood sugar. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 efimosfermin is likely to be safe for humans?

Research has shown that efimosfermin alfa was safe in earlier studies. People with fatty liver disease, particularly metabolic dysfunction-associated steatohepatitis (MASH), tolerated the treatment well. Reports indicated reduced liver fat, suggesting the treatment is both effective and safe. Serious side effects were rare or absent in the studies. This is encouraging for those considering participation in a trial with this treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Researchers are excited about Efimosfermin Alfa for fatty liver disease because it offers a fresh approach compared to existing treatments like lifestyle changes and medications that primarily focus on managing symptoms. Efimosfermin Alfa works by potentially targeting metabolic pathways directly involved in liver fat accumulation, setting it apart from current options. With its novel mechanism of action, this treatment could lead to more effective management of the disease, providing hope for those who don't respond well to conventional therapies.

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

Research has shown that efimosfermin, a long-acting protein that helps control metabolism, may effectively treat fatty liver disease. In an earlier study, 89% of participants experienced at least a 30% reduction in liver fat after 12 weeks of treatment. Other studies have reported significant improvements in liver health, including reduced liver damage and scarring. Patients also showed improvements in resolving metabolic dysfunction-associated steatohepatitis (MASH), a condition related to fatty liver disease. Overall, efimosfermin appears to offer meaningful benefits for those with fatty liver disease. Participants in this trial will receive either efimosfermin at different doses or a placebo to further evaluate its effectiveness. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

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

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

I have a history of type 1 diabetes.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

GlaxoSmithKline Research & Development Limited

Collaborator

Trials

4

Recruited

15,100+

GSK Research and Development Limited

Collaborator

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40484014/

Efimosfermin alfa (BOS-580), a long-acting FGF21 ... At week 12, 47 (89%) of 53 participants receiving efimosfermin for whom data were available had at least a 30% reduction in hepatic fat ...

2. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253%2825%2900067-6/abstract

Efimosfermin alfa (BOS-580), a long-acting FGF21 ... At week 12, 47 (89%) of 53 participants receiving efimosfermin for whom data were available had at least a 30% reduction in hepatic fat ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2468125325000676

Efimosfermin alfa (BOS-580), a long-acting FGF21 ... In participants with phenotypic MASH, efimosfermin had a favourable safety profile and showed improvements in indicators of hepatic steatosis. These results ...

4. natap.org natap.org/2024/AASLD/AASLD_31.htm

Boston Pharmaceuticals to Announce Positive Phase 2 ... In clinical studies, efimosfermin has previously demonstrated statistically significant reductions in liver fat content, markers of liver injury and fibrosis, ...

5. healio.com healio.com/news/hepatology/20241119/monthly-efimosfermin-offers-rapid-meaningful-improvement-for-mash-related-fibrosis

Monthly efimosfermin offers 'rapid, meaningful' ... Patients treated with once-monthly efimosfermin 300 mg achieved significant improvements in metabolic dysfunction-associated steatohepatitis resolution and ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07221227

A Pivotal Clinical Study to Investigate Efimosfermin Alfa in ... The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related ...

7. gsk.com gsk.com/en-gb/media/press-releases/gsk-to-acquire-efimosfermin-a-phase-iii-ready-potential-best-in-class-specialty-medicine-to-treat-and-prevent-progression-of-steatotic-liver-disease-sld/

GSK to acquire efimosfermin, a phase III-ready potential ... Phase II data show potential of efimosfermin to reverse liver fibrosis, demonstrated in metabolic dysfunction-associated steatohepatitis (a form ...