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Efruxifermin

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Efruxifermin
Clinical data
Other namesAKR-001; AMG-876
Legal status
Legal status
  • Investigational
Identifiers
CAS Number
PubChem SID
UNII

Efruxifermin (AKR-001) is an investigational drug developed by Akero Therapeutics, acting as a fibroblast growth factor 21 (FGF21) analog developed to treat metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), and type 2 diabetes.[1][2][3]

Efruxifermin is designed to mimic the biological activity of FGF21, which is a metabolic hormone, primarily produced and secreted by hepatocytes in response to metabolic stressors such as fasting, ketogenic diets, or high carbohydrate intake. Its dysfunction is a key contributor to MASH. FGF21 acts to regulate systemic energy balance, glucose metabolism, and lipid oxidation. It does so by binding to specific fibroblast growth factor receptors (FGFRs)—primarily FGFR1c, FGFR2c, and FGFR3c. However, FGFRs alone have low specificity and affinity for FGF21. They require transmembrane protein β-klotho (KLB) as a co-receptor to enable effective signaling. Efruxifermin acts as an agonist of FGFR1c, FGFR2c, and FGFR3c, with co-activation requiring the presence of KLB, which is consistent with the biological activity of FGF21.[4] [5]

As of beginning of 2025, Efruxifermin is undergoing Phase 3 clinical trials in the SYNCHRONY program, which includes studies targeting both pre-cirrhotic MASH and compensated cirrhosis due to MASH. The SYNCHRONY program builds on results from two 96-week Phase 2b clinical trials, where 39-41% of patients receiving the drug experienced at least a one-stage improvement in fibrosis without worsening of MASH, compared to 15-20% in the placebo group.[5]

References

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  1. ^ Shao, Weijuan; Jin, Tianru (March 2022). "Hepatic hormone FGF21 and its analogues in clinical trials". Chronic Diseases and Translational Medicine. 8 (1): 19–25. doi:10.1016/j.cdtm.2021.08.005. ISSN 2589-0514. PMC 9126297. PMID 35620160.
  2. ^ Carvalho, Thiago (20 June 2023). "Efruxifermin combined with a GLP-1 receptor agonist reduces liver fat in NASH". Nature Medicine. 29 (8): 1881. doi:10.1038/d41591-023-00055-1. PMID 37340082. S2CID 259210572.
  3. ^ Kaufman, Allegra; Abuqayyas, Lubna; Denney, William S.; Tillman, Erik J.; Rolph, Tim (July 2020). "AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients". Cell Reports Medicine. 1 (4): 100057. doi:10.1016/j.xcrm.2020.100057. PMC 7659583. PMID 33205064.
  4. ^ Harrison, Stephen A; Frias, Juan P; Neff, Guy; Abrams, Gary A; Lucas, K Jean; Sanchez, William; Gogia, Sudhanshu; Sheikh, Muhammed Y; Behling, Cynthia; Bedossa, Pierre; Shao, Lan; Chan, Doreen; Fong, Erica; de Temple, Brittany; Shringarpure, Reshma (2023-12-01). "Safety and efficacy of once-weekly efruxifermin versus placebo in non-alcoholic steatohepatitis (HARMONY): a multicentre, randomised, double-blind, placebo-controlled, phase 2b trial". The Lancet Gastroenterology & Hepatology. 8 (12): 1080–1093. doi:10.1016/S2468-1253(23)00272-8. ISSN 2468-1253.
  5. ^ a b "Akero Therapeutics | EFX for MASH | Fc-FGF21 Fusion Protein". Akero. Retrieved 2025-01-29.