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. 

Data from cohort D of Ph2b Symmetry trial (NCT05039450)
Drug and dose Efruxifermin 50mg Placebo P value
N 16 10 -
Mean change from baseline in hepatic fat fraction* (%) -65 -10 <0.001
Proportion of patients achieving a reduction in liver fat of at least 50% (%)
88 0 <0.001
Proportion of patients whose liver fat normalised to 5% or less (%) 88 10 <0.001
*Assessed by MRI-PDFF. All patients on background GLP-1 therapy. Source: company release. 


Selected incretins in development for Nash/Nafld
Company Project Mechanism Trial details
Novo Nordisk Wegovy/Ozempic (sc semaglutide) GLP-1 agonist Essence, Ph3 in Nash, could report 2028
Hanmi Efinopegdutide GLP-1/glucagon agonist Data from Ph2a in Nafld due at Easl, Jun 2023
Boehringer Ingelheim BI 456906 GLP-1/glucagon agonist Ph2 in Nash and fibrosis could report late 2023
Lilly Mounjaro GLP-1/GIP agonist Synergy-Nash, Ph2 in Nash, could report 2024
Hanmi/Merck Efocipegtrutide (HM15211/
LAPS Triple Agonist)
GIP/GLP-1/glucagon agonist Ph2 in Nash could report 2025
Altimmune Pemvidutide GLP-1/glucagon agonist Data from Ph1 in Nafld due at Easl, Jun 2023
Source: Evaluate Pharma, clinicaltrials.gov.

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