Statistically Significant Changes Observed in Multiple NASH-Associated Genes Following Eight Weeks of VK2809 Treatment
Gene Expression Changes Align with Histologic Data Showing Significant Reductions in Fibrosis, Steatosis and NAS
SAN DIEGO, Sept. 11, 2017 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced positive results from a gene expression analysis conducted as part of its recently completed study of VK2809 in an in vivo model of diet-induced non-alcoholic steatohepatitis (NASH). The analysis, which evaluated more than 20,000 genes, demonstrated that eight weeks of treatment with VK2809 led to statistically significant changes in the expression of multiple genes associated with the development and progression of NASH. These findings align with recently reported histologic results from this study, which demonstrated statistically significant improvements in non-alcoholic fatty liver disease activity score (NAS), liver fibrosis, and liver and plasma lipid levels in animals treated with VK2809 relative to vehicle-treated controls.
Top-line data from the analysis include the following changes in the expression of key genes associated with NASH development and progression:
43.7% decrease in SREBF1 expression (p < 0.001), suggesting reduced SREBP1 expression, reduced de novo lipogenesis
64.2% increase in PPARD expression, (p < 0.01), suggesting improved PPARd expression, improved lipid metabolism
336.8% increase in FGF21 expression (p < 0.001), suggesting improved insulin sensitivity
36.3% decrease in COL1A1 expression (p < 0.05), suggesting reduced collagen I production
Significant improvements were also observed in other NASH-related genes of interest, including CYP7A1 (cholesterol metabolism), MAP3K5 (ASK1, oxidative stress), ANXA2 (inflammation), KRT18 (CK-18, cell apoptosis), ACTA2 (aSMA, fibrosis) and LGALS1 (Galectin 1, fibrosis). Detailed results from this study will be presented at the 68th annual meeting of the American Association for the Study of Liver Diseases (AASLD), October 20-24, 2017 in Washington, D.C.
"The changes in gene expression observed following treatment with VK2809 provide further evidence of its potential benefit in the setting of NASH and related diseases," said Brian Lian, Ph.D., chief executive officer of Viking. "As we reported earlier this year, VK2809 demonstrated potent reductions in liver fat, fibrosis, and the NAFLD Activity Score in this model of diet-induced NASH. The genetic analysis results corroborate the histologic data and suggest that VK2809 achieves this activity by modulating the expression of genes associated with lipid metabolism, insulin sensitivity, and fibrosis, all of which are important in the setting of NASH. This breadth of activity highlights VK2809's differentiated mechanism of action and exciting potential therapeutic profile."
The study was designed to evaluate VK2809 dosed orally (10 mg/kg/day) for eight weeks in a mouse model of diet-induced NASH.1 Control cohorts received either vehicle or active control. Animals were biopsied prior to treatment to ensure disease characteristics consistent with the human form of disease, including the presence of fibrosis. Changes in gene expression were evaluated by assessing changes in RNA expression at the conclusion of the experiment, compared with vehicle-treated controls.
