In short
Efimosfermin alfa is an investigational medicine being studied for metabolic dysfunction-associated steatohepatitis (MASH), a progressive liver disease. Two Phase 3 trials are currently authorised, together planning to enrol 2,450 participants with F2- or F3-stage fibrosis. A Phase 2a trial in 65 participants showed that efimosfermin alfa 300 mg once every 4 weeks improved fibrosis without worsening MASH in 45% of participants, compared with 21% on placebo.
Key points
- Efimosfermin alfa is an engineered fibroblast growth factor 21 (FGF21) analogue designed for once-monthly dosing.
- Two Phase 3 trials are authorised, together planning to enrol 2,450 participants with F2- or F3-stage MASH.
- In a Phase 2a trial, efimosfermin alfa 300 mg every 4 weeks led to fibrosis improvement without worsening MASH in 45% of participants, versus 21% with placebo.
- The most common side effects in earlier studies were gastrointestinal, including nausea, diarrhoea and vomiting, mostly mild to moderate.
- One Phase 3 trial measures fibrosis improvement and MASH resolution at Week 52, and liver-related clinical outcomes over up to 48 months.
- Efimosfermin alfa is given by subcutaneous injection.
What is efimosfermin alfa?
Efimosfermin alfa is an engineered variant of fibroblast growth factor 21 (FGF21), a protein that occurs naturally in the body. It was designed to have a prolonged half-life, which means it stays in the body longer than natural FGF21 and can be given less often. The substance was formerly known as BOS-580. Efimosfermin alfa is an investigational medicine, meaning it has not yet been approved for general use and is being studied in clinical trials.
How does efimosfermin alfa work?
Efimosfermin alfa is a long-acting analogue of FGF21. FGF21 is a hormone-like protein involved in regulating metabolism, including how the body handles fats and sugars. By mimicking FGF21, efimosfermin alfa is intended to act on metabolic pathways that contribute to liver inflammation and fibrosis in MASH. The extended half-life allows for once-monthly dosing.
Which conditions is it studied for?
- Metabolic dysfunction-associated steatohepatitis (MASH) — a progressive liver disease characterised by fat accumulation, inflammation and fibrosis (scarring) in the liver. Both Phase 3 trials enrol participants with biopsy-confirmed or suspected F2- or F3-stage fibrosis, meaning moderate to advanced liver scarring.
How is efimosfermin alfa given?
Efimosfermin alfa is given by subcutaneous injection, which means it is injected under the skin. In the Phase 2a trial, doses ranged from 75 mg to 300 mg, given either once every 2 weeks or once every 4 weeks. The Phase 2 trial used a dose of 300 mg every 4 weeks.
What do the clinical trials show?
Two Phase 3 trials of efimosfermin alfa are authorised. One trial (NCT07221227) plans to enrol 1,200 participants with biopsy-confirmed F2- or F3-stage MASH. It measures the proportion of participants with fibrosis improvement of at least one stage without worsening of steatohepatitis at Week 52, the proportion with resolution of steatohepatitis without worsening of fibrosis at Week 52, and the time to liver-related clinical outcomes over up to 48 months. The second trial (NCT07221188) plans to enrol 1,250 participants with known or suspected F2- or F3-stage MASH and focuses on safety and tolerability, including treatment-emergent adverse events and laboratory abnormalities at Week 52.
Earlier clinical research provides efficacy data. In a randomised, double-blind, placebo-controlled Phase 2 trial of 65 evaluable participants with MASH and biopsy-confirmed F2/F3 fibrosis, efimosfermin alfa 300 mg every 4 weeks led to fibrosis improvement of at least one stage without worsening of MASH in 45% of participants, compared with 21% on placebo. MASH resolution without worsening of fibrosis was seen in 68% of participants on efimosfermin alfa versus 29% on placebo. A Phase 2a trial tested doses from 75 mg to 300 mg in participants with phenotypic MASH.
What side effects are known?
In the Phase 2 safety analysis, the most frequent side effects were gastrointestinal. Nausea occurred in 33% of participants on efimosfermin alfa compared with 13% on placebo, diarrhoea in 23% versus 8%, and vomiting in 16% versus 3%. These side effects were mostly mild to moderate. The rate of discontinuations due to side effects in the efimosfermin alfa arm was 4.7%.