Once-Monthly Efimosfermin Alfa Shows Promise for MASH in Phase 2 Study

New phase 2 data suggest once-monthly efimosfermin alfa (BOS-580) may be a promising treatment for metabolic dysfunction-associated steatohepatitis (MASH).1

Findings presented at Digestive Disease Week (DDW) 2025 showed treatment with the fibroblast growth factor 21 (FGF21) analogue resulted in MASH resolution and fibrosis improvement at 24 weeks in patients with F2/F3 fibrosis due to MASH.1

“FGF21 is one of the most effective mechanisms in MASH,” Mazen Noureddin, MD, MHSc, professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute, explained to HCPLive, citing its roles in metabolism, inflammation, and fibrosis, as well as its long half-life allowing once-monthly administration of the drug.1

In a phase 2a multiple dose/regimen study, efimosfermin alfa significantly improved liver steatosis, markers of liver injury, and fibrosis in subjects with phenotypic MASH. In a subsequent phase 2, randomized, double-blind, placebo-controlled study, 84 patients with biopsy-confirmed MASH and F2/F3 fibrosis and NAS ≥4 were randomly assigned in a 1:1 ratio to receive once-monthly efimosfermin 300mg (n = 43) or placebo (n = 41) for 24 weeks.1

The primary endpoint was safety and tolerability, while exploratory objectives included the proportion of subjects achieving fibrosis improvement ≥1 stage without worsening of MASH, MASH resolution without worsening of fibrosis, ≥2 point improvement in the NAS score, and a composite endpoint of fibrosis improvement ≥1 stage and MASH resolution.1

Among the cohort, the majority (52.4%) of patients were female with a mean age of 54 years. F3 fibrosis was observed in 43% of patients, and 57% had type 2 diabetes.1

Findings presented at DDW showed that in the biopsy analysis set, a greater higher proportion of patients treated with efimosfermin 300mg (n = 34) achieved improvement in fibrosis without worsening of MASH (45.2% vs 20.6%; P = .038), and resolution of MASH without worsening of fibrosis (67.7% vs 29.4%; P = .002) compared with placebo (n = 31).1

Additionally, a significantly greater proportion of patients achieved MASH improvement with ≥2 point improvement in the NAS score without worsening of fibrosis (67.7% vs 20.6%; P <.001). The proportion of patients who achieved the composite endpoint of ≥1 stage fibrosis improvement and MASH resolution was 38.7% for efimosfermin 300 mg and 17.6% for placebo (P = .066).1

In both groups, the most frequent treatment-related adverse events (AEs) were mild to moderate gastrointestinal events of nausea, diarrhea and vomiting. Investigators noted discontinuations were balanced, with only 2 efimosfermin patients who discontinued due to low-grade AEs and a single treatment-related grade 3 serious AE.1

As described in a press release from Boston Pharma, the phase 2 clinical development program of efimosfermin is continuing with an open-label extension in F2 and F3 MASH patients, providing an additional 24 weeks of treatment to assess long-term safety and efficacy up to 48 weeks. The company also plans to initiate a supplemental study in F4 MASH.2

Editors’ note: Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others.

References

1. Noureddin M, Kowdley KV, Clawson A, et al. ONCE-MONTHLY EFIMOSFERMIN ALFA (BOS-580) IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS WITH F2/F3 FIBROSIS: RESULTS FROM A 24 WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 TRIAL. Abstract presented at Digestive Disease Week 2025 in San Diego, CA, from May 3 - May 6, 2025.

2. Boston Pharma. Boston Pharmaceuticals to Present State-of-the-Art Lecture and Poster for Once-monthly Efimosfermin Alfa at Digestive Disease Week® 2025. April 23, 2025. Accessed May 5, 2025. https://www.businesswire.com/news/home/20250423472313/en/Boston-Pharmaceuticals-to-Present-State-of-the-Art-Lecture-and-Poster-for-Once-monthly-Efimosfermin-Alfa-at-Digestive-Disease-Week-2025