A phase IIb randomised-controlled trial of the FFAR1/FFAR4 agonist icosabutate in MASH

With expression on multiple cell types regulating both glycaemic control and liver inflammation, targeting free fatty acid receptors (FFAR)1 and 4 could offer an attractive approach for the treatment of both fibrosing metabolic dysfunction-assoicated steatohepatitis (MASH) and its comorbidities. Although treatment of patients with MASH and F1-F3 fibrosis with oral icosabutate (a FFAR1/FFAR4 agonist) did not meet the pre-defined primary endpoint (MASH resolution without worsening of fibrosis), the overall dataset (including AI-assisted digital pathology) suggest an improvement in fibrosis in treated patients. Improvements in multiple biomarkers of liver damage, inflammation and glycaemic control were observed in response to therapy. Icosabutate was generally safe and well tolerated, and the overall data support further testing of icosabutate in patients with MASH, in particular those with more advanced disease (F2-F3 fibrosis) and type 2 diabetes.