Akero suggests the limits of GLP-1s in Nash

Adding efruxifermin to background GLP-1 therapy cut nonalcoholic steatohepatitis patients’ liver fat, Akero said today. But the implication is not so much that efruxifermin might be a contender in Nash as that GLP-1s alone might not. The data come from the small expansion cohort of Akero’s mid-stage Symmetry Nash trial, comprising patients with both liver fibrosis caused by Nash and type 2 diabetes, who were already taking a GLP-1 for the latter condition. The significant improvement in liver fat among those given Akero’s FGF21 analogue versus the placebo group suggests that the GLP-1s the patients were on were doing little to improve the condition of their livers. Novo Nordisk’s juggernaut semaglutide hit in phase 2 in Nash but failed to resolve fibrosis, and a phase 3 Nash trial, Essence, is ongoing. Another important finding from Symmetry was that efruxifermin plus the GLP-1 was generally safe; since many Nash patients are also diabetic or obese any additional toxicity could have limited Akero’s market. Perhaps GLP-1/glucagon co-agonists can do better in Nash than GLP-1s. Several are in trials in Nash or the milder condition nonalcoholic fatty liver disease, including Lilly’s Mounjaro. Meanwhile full Symmetry data should come later this year.