Viking Therapeutics Announces Results of Gene Expression Analysis from In Vivo Study of VK2809 in Non-Alcoholic Steatohepatitis (NASH)
- Category: Small Molecules
- Published on Monday, 11 September 2017 18:22
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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, CA, USA I September 11, 2017 I Viking Therapeutics, Inc. ("Viking") (NASDAQ: 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 PPARδ 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 (αSMA, 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.
VK2809 is a novel, orally available small molecule thyroid receptor beta (TRβ) agonist that possesses selectivity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of lipid disorders. Viking is currently evaluating VK2809 in a randomized, double-blind, placebo-controlled, parallel group Phase 2 study designed to assess the drug candidate's efficacy, safety and tolerability in patients with elevated LDL-C and non-alcoholic fatty liver disease. Previously reported clinical data have demonstrated that treatment with VK2809 leads to significant reductions in plasma triglycerides, LDL cholesterol (LDL-C), and atherogenic protein levels in subjects with mild hypercholesterolemia.
About Viking Therapeutics, Inc.
Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders. The company's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. Viking has exclusive worldwide rights to a portfolio of five therapeutic programs in clinical trials or preclinical studies, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated. The company's clinical programs include VK5211, an orally available, non-steroidal selective androgen receptor modulator, or SARM, in Phase 2 development for the treatment and prevention of lean body mass loss in patients who have undergone hip fracture surgery, VK2809, a small molecule thyroid beta agonist in Phase 2 development for hypercholesterolemia and fatty liver disease, and VK0612, a first-in-class, orally available drug candidate in Phase 2 development for type 2 diabetes. Viking is also developing novel and selective agonists of the thyroid beta receptor for adrenoleukodystrophy, as well as two earlier-stage programs targeting metabolic diseases and anemia.
1. N.M. Kristiansen, S.S. Veidal, et al., Obese diet-induced mouse models of non-alcoholic steatohepatitis-tracking disease by liver biopsy, World J. Hepatology, 2016; 8(16):673-684. M. Reigh, K.S. Tobol, et al., Comparative effects of liraglutide, elafibranor, and obeticholic acid on NAFLD activity score and fibrosis stage in a diet-induced obese mouse model of biopsy-confirmed NASH; Hepatology 66(1): S599, 2017.
SOURCE: Viking Therapeutics