BOSTON — In this exclusive video from The Liver Meeting 2019, Manu Chakravarthy, MD, PhD, chief medical officer and senior vice president of Axcella Health, discusses positive study results from two product candidates including one for nonalcoholic fatty liver disease and one for cirrhosis.
Chakravarthy first described the study of AXA1125, which comprised 32 patients with NAFLD and type 2 diabetes.
After 12 weeks of treatment, AXA1125 induced branched-chain amino acid catabolism supported by increased plasma C5-OH/C3-DC, improved insulin sensitivity supported by enhanced insulin-dependent glucose uptake in primary hepatocytes, and coordinated effects to dampen the inflammatory and fibrogenic responses as manifested by decreased proinflammatory and fibrogenic markers
Chakravarthy next described the study of AXA1665 for patients with mild to moderate hepatic insufficiency. Investigators enrolled 16 patients in the crossover study, in which they received either a high or a low dose of AXA1665 each for 15 days on the background of a controlled high protein diet, late evening snack, and physical activity in a domiciled setting.
High doses of AXA1665 led to restoration of amino acid dysregulation by promoting anabolism-associated amino acids, such as leucine, while concomitantly enhancing clearance of ammoniagenic aromatic amino acids, such as phenylalanine and tyrosine, which have been inversely related to health consequences in patients with cirrhosis.
AXA1665 high dose administration also led to dampened ammoniagenesis as indicated by reduced fasted plasma ammonia concentration, and increased ureagenesis as reflected by increased fasted blood urea nitrogen.
“Together, these studies provide us good insight to move our programs into later stage studies, which we are very excited to undertake in 2020,” Chakravarthy told Healio Gastroenterology and Liver Disease.
Chakravarthy M, et al. Abstract 2134. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Comb W, et al. Abstract 0432. Presented at: The Liver Meeting; Nov. 7-12, 2019; Boston.
Disclosure: Chakravarthy is the chief medical officer and senior vice president of Axcella Health.
Editor's note: This article has been updated with corrected information from Axcella Health.