Manage Metabolic Dysfunction-Associated Steatohepatitis with Efruxifermin
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on July 11th, 2025
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As the frequency of obesity increases in Vietnam, physicians need to prepare for a paired increase in metabolic dysfunction-associated steatohepatitis (MASH) cases. Beside dietary interventions and lifestyle modification, there are some viable therapies in the form of GLP-1 agonists and resmetiron; however, there is an increased need for other treatments to treat patients who cannot be treated with the remaining options. With funding from Akero Therapeutics, a study was conducted to evaluate the usage of efruxifermin to manage MASH.
The phase 2 clinical trial included 181 participants with an average age of 60 years old who had been diagnosed with metabolic dysfunction-associated steatohepatitis. Additionally, these patients also experienced decompensated cirrhosis with a Child-Pugh score between 5 or 6. Clinical assessment for inflammation, steatosis, and ballooning with the NAFLD activity scale yields an average score of 3.9, with 8 being the most severe form of disease. Baseline biochemical marker analysis was performed yielding an average alanine aminotransferase and aspartate aminotransferase concentration of 39.6 and 36.7 U/liter, respectively.
The participants were randomly assigned to be treated with either placebo or efruxifermin. The subcutaneous injection was administered once every week, and two dose levels of efruxifermin were tested: 28 mg and 50 mg. Efruxifermin is a fibroblast growth factor 21 (FGF21) analogue, and previous study had found that FGF21 can regulate glucose and lipid metabolism. With its antifibrotic property, the medication is hypothesized to be able to dampen the fibrogenesis process in hepatocytes.
After 96 weeks of treatment, the researchers found that 29% of the patients treated with 50 mg of efruxifermin experienced at least one stage of fibrosis reduction. This clinical benefit is observed to a lesser extent at 20% in the 28 mg group. Additionally, efruxifermin also resulted in significant reduction in LDL cholesterol and liver-stiffness, as measured by transient elastography. A reduction in alanine aminotransferase and aspartate aminotransferase was also recorded after 16 weeks of treatment and sustained over the period of the study, but this difference is inconclusive. Safety analysis found that discontinuation due to adverse effects was higher in patients treated with 50 mg of efruxifermin, and gastrointestinal irritation was most frequently reported. The study noted that 27% of the participants were treated with GLP-1 receptor agonists, but the distribution of medication usage between the 3 treatment groups varied, and there were no subgroup analyses to explore this factor.
The phase 2 clinical trial included 181 participants with an average age of 60 years old who had been diagnosed with metabolic dysfunction-associated steatohepatitis. Additionally, these patients also experienced decompensated cirrhosis with a Child-Pugh score between 5 or 6. Clinical assessment for inflammation, steatosis, and ballooning with the NAFLD activity scale yields an average score of 3.9, with 8 being the most severe form of disease. Baseline biochemical marker analysis was performed yielding an average alanine aminotransferase and aspartate aminotransferase concentration of 39.6 and 36.7 U/liter, respectively.
The participants were randomly assigned to be treated with either placebo or efruxifermin. The subcutaneous injection was administered once every week, and two dose levels of efruxifermin were tested: 28 mg and 50 mg. Efruxifermin is a fibroblast growth factor 21 (FGF21) analogue, and previous study had found that FGF21 can regulate glucose and lipid metabolism. With its antifibrotic property, the medication is hypothesized to be able to dampen the fibrogenesis process in hepatocytes.
After 96 weeks of treatment, the researchers found that 29% of the patients treated with 50 mg of efruxifermin experienced at least one stage of fibrosis reduction. This clinical benefit is observed to a lesser extent at 20% in the 28 mg group. Additionally, efruxifermin also resulted in significant reduction in LDL cholesterol and liver-stiffness, as measured by transient elastography. A reduction in alanine aminotransferase and aspartate aminotransferase was also recorded after 16 weeks of treatment and sustained over the period of the study, but this difference is inconclusive. Safety analysis found that discontinuation due to adverse effects was higher in patients treated with 50 mg of efruxifermin, and gastrointestinal irritation was most frequently reported. The study noted that 27% of the participants were treated with GLP-1 receptor agonists, but the distribution of medication usage between the 3 treatment groups varied, and there were no subgroup analyses to explore this factor.