Visual Abstract

Background: AXA1125, an investigational composition of 5 amino acids and n-acetyl-cysteine, targets multiple biologies relevant to NAFLD pathogenesis.

Methods: Primary human hepatocytes (PHH) from multiple donors were pretreated with AXA1125 components (LIVRQNac), exposed to lipotoxic insult in the presence of LIVRQNac, incubated in high glucose insulin-free medium, followed by glucose-free medium±insulin. Human safety, tolerability, and biologic activity were evaluated in a 16-week, multicenter, randomized, placebo (Pbo)-controlled study (NCT04073368) in subjects with NAFLD±T2D. Results from Pbo and AXA1125 24 g twice daily dosing in subjects with T2D are reported.

Results: In PHH, LIVRQNac reduced glucose output by ~50% (p <0.01) and enhanced insulin-dependent Akt phosphorylation by 80% (p<0.001). Clinically, AXA1125 showed greater reductions from BL at W16 vs. Pbo in metabolic and fibroinflammatory biomarkers (Table); both arms had similar baseline characteristics. AEs were mostly mild to moderate.

Conclusions: This concordant multifactorial biologic activity, including the effects on glucose homeostasis, suggests a potential enhanced impact of AXA1125 in NAFLD subjects with diabetes that warrants further investigation.

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Disclosure

S. Baum: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. J. Zhao: Employee; Self; Axcella Health Inc., Stock/Shareholder; Self; Axcella Health Inc. M. Chakravarthy: None. M. Koziel: None. S. A. Harrison: Consultant; Self; Axcella Health Inc. N. T. Gunn: None. Z. Younes: Research Support; Self; Axcella Health Inc., Novo Nordisk. A. Kohli: Research Support; Self; Axcella Health Inc., Novo Nordisk. R. Patil: Speaker’s Bureau; Self; Intercept Pharmaceuticals, Inc. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. M. Hamill: Employee; Self; Axcella Health Inc. N. Daou: None.

Funding

Axcella Health Inc.

© 2021 by the American Diabetes Association
2021
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