Efimosfermin alfa is a long-acting, once-monthly fibroblast growth factor 21 (FGF21) analogue with an extended half-life of 21 days. In a phase 2a multiple dose/ regimen study, efimosfermin alfa led to significant improvements in liver steatosis, markers of liver injury, and fibrosis among patients with MASH.1 Noureddin and colleagues presented results of the histologic assessment of a randomized, double-blind phase 2b study comparing efimosfermin alfa 300 mg once monthly vs placebo.2
To be eligible for the study, patients were required to have biopsyconfirmed MASH with F2 and F3 fibrotic stage. The primary endpoint was safety and tolerability; histologic endpoints were also evaluated, including fibrosis improvement of 1 or more stages without worsening of MASH, MASH resolution without worsening of fibrosis, and fibrosis improvement together with MASH resolution. A total of 84 patients were randomized, with 67 completing study treatment. Baseline characteristics were well balanced between the efimosfermin alfa and placebo arms, with the exception of a higher proportion of patients with diabetes in the efimosfermin alfa group.
Efimosfermin alfa represents an attractive new therapeutic target for MASH with fibrosis, given its mechanism of action as an FGF21 agonist, and the fact that it can be dosed monthly. The results of thii phase 2 trial demonstrated high efficacy on fibrosis regression and MASH resolution after a relatively short duration of treatment, providing confidence for taking this drug into phase 3 development.
— Naim Alkhouri, MD
Efimosfermin alfa, compared with placebo, achieved statistically significant improvements at week 24 in MASH resolution without worsening of fibrosis (68% vs 29%; P<.01) and fibrosis improvement without worsening of MASH (45% vs 21%; P<.01), as shown in Figure 7. Several biomarkers were also improved with efimosfermin alfa, including MRI-PDFF reduction as well as clinically meaningful glycemic control markers such as glycated hemoglobin.
Figure 7.
Effects of once-monthly efimosfermin alfa treatment at 24 weeks in patients with biopsy-confirmed MASH and F2/F3 fibrosis. MASH, metabolic dysfunction- associated steatohepatitis. Adapted from Noureddin M, et al. AASLD abstract 5017. Presented at: The Liver Meeting; November 15-19, 2024; San Diego, CA.2
Efimosfermin alfa was associated with a favorable safety profile; one grade 3 treatment-related AE was reported. Low rates (<5%) of changes in appetite were reported with efimosfermin alfa, and no weight gain was apparent. Few (<5%) injection site reactions occurred.
References
- Bain G, Clawson A, Lopez-Talavera JC, Odrljin T. BOS-580, a long-acting FGF21 analogue, treatment shows beneficial changes in the circulating lipidome and improves MASEF score in patients with phenotypic metabolic dysfunction-associated steatohepatitis in a phase 2a randomized, placebo-controlled, 12-week study [EASL abstract 621]. J Hepatol. 2024;80(suppl 1) [Google Scholar]
- Noureddin M, Kowdley K, Clawson A Once-monthly efimosfermin alfa (BOS-580) in metabolic dysfunction-associated steatohepatitis with F2/F3 fibrosis: results from a 24 week, randomized, doubleblind, placebo-controlled, phase 2 trial [AASLD abstract 5017]. Presented at: The Liver Meeting; November 15-19, 2024; San Diego, CA.