Viking Therapeutics Announces Presentation Of Data From In Vivo Proof-Of-Concept Study Of VK2809 In Glycogen Storage Disease Ia (GSD Ia) At The 13th International Congress Of Inborn Errors Of Metabolism (ICIEM)
Published: Sep 07, 2017
SAN DIEGO, Sept. 7, 2017 /PRNewswire/ -- 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 the presentation of positive final results from a proof-of-concept study of VK2809 in an in vivo model of glycogen storage disease type Ia (GSD Ia). GSD Ia is a rare, orphan genetic disease that results in excess accumulation of glycogen and lipids in liver tissue. The study results demonstrated that treatment with VK2809 produced statistically significant reductions in liver triglyceride content and liver weight compared with vehicle-treated controls. Final results from the study were summarized in a poster titled, "Evaluation of the Thyroid Hormone Agonist VK2809 in an In Vivo Model of Glycogen Storage Disease Type Ia," presented today at the 13th International Congress of Inborn Errors of Metabolism (ICIEM), in Rio De Janeiro, Brazil.
In this study, treatment with VK2809 led to statistically significant reductions in key metabolic markers of GSD Ia after just four days, highlighting the molecule's potent, rapid-acting effect in liver tissue. Researchers utilized the glucose-6-phosphatase (G6PC) knockout mouse model, which is intended to replicate the impairment of this enzyme's activity in patients with GSD Ia. Highlights of the data presented today include:
- Mean total liver triglycerides were reduced by 69.0% in VK2809-treated animals relative to vehicle-treated control animals (p < 0.0001). Total liver triglyceride content in VK2809-treated animals was reduced to within the range of the study's wild type control mice (e.g. mice that did not possess the genetic signature of GSD Ia).
- Mean liver weights were reduced by 35.7% in VK2809-treated animals as compared to controls (p < 0.05). Liver weights in treated animals were reduced to within the range of wild type controls.
- Mean liver triglyceride concentration was reduced by 54.0% (p = 0.07).
In addition, liver mass as a percent of body mass was significantly reduced among treated animals compared with controls (p < 0.05), in line with the expected benefit of VK2809. Additional evaluation of VK2809 on markers of autophagy and genes associated with lipid metabolism in this model is ongoing.
"The data presented at ICIEM confirm and expand upon the initial findings from this study which we reported earlier this year. The rapid observed reductions in total liver triglyceride content resulting from treatment with VK2809 suggest an encouraging potential profile for patients who experience complications of GSD Ia, such as hepatic steatosis. Total liver triglycerides in VK2809-treated animals were reduced to within the range observed in normal mice, demonstrating VK2809's ability to potentially alleviate certain abnormalities associated with poor metabolic control," said Brian Lian, Ph.D., chief executive officer of Viking. "These findings support our plan to file an IND later this year to advance VK2809 into a proof-of-concept study in patients with GSD Ia. We believe VK2809's novel liver-targeting mechanism, combined with prior data showing robust effects on plasma triglycerides in humans, represent a potential approach to improving steatosis and metabolic control in patients with GSD Ia. In addition, our recent data demonstrating anti-fibrotic benefits from VK2809 may be relevant to other glycogen storage diseases and we plan to further explore potential applications in these settings."
GSD Ia is characterized by an inability to metabolize glucose precursors, resulting in hypoglycemia and increased lipogenesis. The disease is caused by mutations in the gene for G6PC, a critical enzyme involved in the production of glucose from either glycogen or gluconeogenesis. Impaired G6PC function leads to dramatically elevated liver triglyceride levels in human patients and in animal models of the disease. In patients, this may contribute to serious long-term complications, such as severe hepatomegaly, hepatic adenomas, and hepatocellular carcinoma. Manifestations of the disease begin to appear shortly after birth and continue through adolescence into adulthood. There is currently no approved therapy for GSD Ia. VK2809's potential to rapidly reduce hepatic triglyceride levels, as demonstrated in this initial evaluation in a GSD Ia model, provide support for the continued investigation of the compound in this indication.
The proof-of-concept study was conducted under a sponsored research agreement between Duke University and Viking Therapeutics and designed to evaluate the effects of VK2809 in Duke University's G6PC knockout mouse model. The G6PC knockout model is intended to replicate many of the same biochemical and physiological characteristics present in GSD Ia patients. In addition to the G6PC knockout mice, researchers also included wild type mice in the study to provide additional points of comparison. Study mice, both G6PC knockout and wild type, received VK2809 or vehicle once-daily and subsequently evaluated for changes in various measures of disease, including liver size, weight, and triglyceride content.
VK2809 is a novel, orally available small molecule thyroid receptor beta (TR) 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 GSD Ia
Glycogen storage disease Ia (GSD Ia) is a rare, orphan genetic disease caused by a deficiency of glucose-6-phosphatase (G6PC), an enzyme responsible for the liver's production of free glucose from glycogen and gluconeogenesis. The disease, for which there is no approved treatment, results in an excess accumulation of glycogen and lipids in the liver, potentially leading to hepatosteatosis, liver failure, development of hepatic adenomas, and hepatocellular carcinoma. Increased triglyceride production and elevated hepatic triglyceride levels are characteristic of GSD Ia and associated with many manifestations of the disease. GSD Ia is estimated to occur in approximately 1 in every 50,000 100,000 births in the United States. As manifestations of the disease begin to present themselves at birth, a sizeable portion of GSD Ia patients are children.
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 non-alcoholic 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 GSD Ia and X-linked adrenoleukodystrophy, as well as two earlier-stage programs targeting metabolic diseases and anemia.
Follow Viking on Twitter @Viking_VKTX.
This press release contains forward-looking statements regarding Viking Therapeutics, including statements about Viking's expectations regarding its development activities, timelines and milestones, as well as the company's goals and plans regarding VK2809 and VK2809's prospects. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of Viking's product candidate development activities and clinical trials, including those for VK2809; risks that prior clinical and pre-clinical results may not be replicated; and risks regarding regulatory requirements, among others. These forward-looking statements speak only as of the date hereof. Viking disclaims any obligation to update these forward-looking statements.
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