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. https://www.evaluate.com/vantage/articles/news/trial-results-snippets/akero-suggests-limits-glp-1s-nash