Efruxifermin and MASH

Efruxifermin (EFX) is a promising treatment for metabolic dysfunction-associated steatohepatitis (MASH), a severe progression of metabolic liver disease with limited effective therapies. EFX is a fibroblast growth factor 21 (FGF21) analogue that offers dual benefits for both liver and metabolic health. It works by regulating lipids, improving insulin sensitivity, and reducing inflammation.

In a systematic review of four phase 2 clinical trials involving 450 participants with biopsy-confirmed MASH, EFX was evaluated for its safety and efficacy. Administered weekly via subcutaneous injection at doses of 28 mg or 50 mg, EFX showed significant improvements in liver health and metabolic parameters over 12 to 96 weeks.

EFX reduced liver enzyme levels (ALT, AST, GGT) and hepatic fat fraction (HFF) by 54% to 62%, with some patients achieving complete normalization of liver fat. It also improved liver fibrosis and resolved MASH in many cases. Non-invasive markers of fibrosis, such as ELF scores and liver stiffness, showed notable reductions, confirming its antifibrotic effects.

Metabolically, EFX improved HbA1c, insulin resistance, triglycerides, LDL-C, and increased HDL-C and adiponectin. The 50 mg dose led to modest weight loss, while the 28 mg dose focused on metabolic improvements without significant weight changes.

Though EFX caused mild-to-moderate gastrointestinal side effects like nausea and diarrhea, it was generally well-tolerated. Compared to other therapies like GLP-1 receptor agonists, EFX demonstrated stronger effects on liver histology and fibrosis.

Efruxifermin offers a comprehensive therapeutic approach for MASH, addressing liver, metabolic, and inflammatory aspects, making it a leading candidate for future treatment. Phase 3 trials are ongoing to confirm its long-term benefits.