897-P: Insulin-Sensitizing Effects of Efruxifermin Improve Glycemic Control in Patients with MASH and Type 2 Diabetes
Authors: LUCAS K J. , HARRISON STEPHEN A. , CHAN DOREEN , TILLMAN ERIK J. , MOULTON ALI , DE TEMPLE BRITTANY , ZARI ARIAN , SHRINGARPURE RESHMA , ROLPH TIMOTHY , CHENG ANDREW , YALE KITTY 
Published: June 2024

Introduction & Objective: In phase 2 studies, efruxifermin (EFX), a long-acting bivalent Fc-FGF21 analog, significantly reduced steatohepatitis and fibrosis in patients with metabolic dysfunction-associated steatohepatitis (MASH). Many patients with MASH have type 2 diabetes (T2D), which is increasingly treated with glucagon-like peptide-1 receptor agonists (GLP-1RAs). We investigated the effects of EFX in patients with T2D, including those being treated with GLP-1RAs.
Methods: The effects of EFX on markers of insulin sensitivity and glycemic control were studied in 5 independent cohorts of patients with T2D and MASH with liver fibrosis, ranging from F1 to F4 (compensated cirrhosis). EFX treatment ranged from 12 to 36 weeks. Endpoints included changes in markers of glucose metabolism and insulin sensitivity, lipoprotein profile, steatohepatitis, and fibrosis, as well as use of T2D medications.
Results: EFX consistently improved markers of insulin sensitivity and glucose metabolism on top of stable T2D therapies, including GLP-1RA. EFX was also associated with a trend towards weight loss. Markers of liver injury, steatohepatitis, and fibrosis were improved consistently by EFX, even in patients on stable GLP-1RA therapy. EFX was safe and well tolerated in all trials; the most common AEs were mild-moderate gastrointestinal events.
Conclusions: EFX has consistently improved markers of whole-body glucose and lipid metabolism in patients with MASH and T2D, even on top of stable T2D medications including GLP-1RA. EFX-mediated insulin sensitization may potentiate effects of insulin or insulin secretagogues, possibly enabling patients to reduce use of insulin and/or other T2D medications to mitigate weight gain, incidence of hypoglycemia, or other side effects.

Disclosure
K.J. Lucas: Research Support; Akero Therapeutics, Inc. S.A. Harrison: Other Relationship; Akero Therapeutics, Inc. Consultant; 89bio, Inc., Agilos Therapeutics. Other Relationship; Altimmune Inc. Advisory Panel; Arrowhead Pharmaceuticals, Inc. Consultant; Asteroid Therapeutics, Bluejay Therapeutics. Research Support; Bristol-Myers Squibb Company. Consultant; BOEHRINGER INGELHEIM PHARMA, INC, Boxer Capital. Advisory Panel; Chronwell Inc. Consultant; Corcept Therapeutics, ECCOGENE, INC, DEXCOM, INC. Advisory Panel; ECHOSENS NORTH AMERICA, INC. Consultant; Enyo Pharma. Other Relationship; GALECTIN THERAPEUTICS, INC. Consultant; GALECTO, INC, HEPAGENE THERAPEUTICS. Other Relationship; HEPION PHARMACEUTICALS, INC, Gilead Sciences, Inc. Consultant; GlaxoSmithKline plc. Other Relationship; Hepta Bio. Consultant; HISTOINDEX PTE. LTD. Advisory Panel; Humana. Other Relationship; Madrigal Pharmaceuticals, Inc., Intercept Pharmaceuticals, Inc. Advisory Panel; Inventiva Pharma. Other Relationship; Ionis Pharmaceuticals, Medpace. Stock/Shareholder; MGGM THERAPEUTICS LLC. Consultant; NEUROBO PHARMACEUTICALS INC. Other Relationship; NGM BIOPHARMACEUTICALS, INC, NORTHSEA THERAPEUTICS B.V., Novo Nordisk. Research Support; Pfizer Inc. Consultant; PIPER SANDLER & CO. Other Relationship; POXEL. Consultant; Regeneron Pharmaceuticals Inc. Other Relationship; Sagimet Biosciences, Sonic Incytes. Consultant; Takeda Canada. Other Relationship; Terns Pharmaceuticals. Consultant; TRAMONTANE THERAPEUTICS INC (Kriya). Other Relationship; Viking Therapeutics. Consultant; CALIMETRIX, LLC. D. Chan: Employee; Akero Therapeutics, Inc. E.J. Tillman: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. A. Moulton: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. B. de Temple: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. A. Zari: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. R. Shringarpure: Employee; Akero Therapeutics, Inc. Stock/Shareholder; Akero Therapeutics, Inc. T. Rolph: Stock/Shareholder; Akero Therapeutics, Inc., Pfizer Inc. A. Cheng: Employee; Akero Therapeutics, Inc. K. Yale: Employee; Akero Therapeutics, Inc.

Funding
Akero Therapeutics Inc