The study was a randomized, double-blind, placebo-controlled Phase 1b trial designed to evaluate the safety, tolerability and pharmacokinetics of a range of VK2809 doses in 56 subjects with elevated serum cholesterol (n = 6 per drug-treated cohort). Following 14 days of VK2809 treatment, subjects experienced statistically significant placebo-adjusted, least square mean reductions in both Lp(a) and apo B across a range of doses. Reductions in apo B ranged from 20.2% at 5 mg (p = 0.0008) to 39.6% at 40 mg (p < 0.0001); reductions in Lp(a) ranged from 31.6% at 5 mg (p = 0.12) to 54.9% at 20 mg (p = 0.002). Comparable results were obtained with or without least square mean adjustments, which account for covariates in patient characteristics.
The therapeutic importance of reducing atherogenic proteins has been highlighted in scientific literature. A report published in the Mayo Clinic Proceedings stated that Lp(a) was an independent, causal, risk factor for atherosclerosis, and that epidemiologic data show a continuous association between Lp(a) and CVD that is multiplied when both LDL-C and Lp(a) are elevated.1 Similarly, determination of apo B levels has been characterized as superior to any other cholesterol index to identify increased risk of CVD and assess the efficacy of lipid-lowering treatment.2 Thus, robust reductions of both Lp(a) and apo B, as demonstrated by VK2809 in this study, may add to the benefits of LDL-lowering therapy by further improving a patient's cardiovascular risk profile.
"These data support the promise of thyroid beta-targeted approaches for the treatment of cardiovascular and other metabolic diseases. We previously reported results showing VK2809's ability to rapidly reduce plasma LDL-C and triglycerides by up to 41% and 79%, respectively, following just 14 days of treatment," said Brian Lian, Ph.D., chief executive officer of Viking. "Today's announcement highlights the added benefit of VK2809 on reducing key proteins associated with elevated cardiovascular risks. The combined benefits from reducing both LDL-C and atherogenic proteins suggest a differentiated therapeutic profile, which may result in improved long-term benefits for patients with lipid or other metabolic abnormalities, including fatty liver disease. We look forward to the results of our ongoing Phase 2 trial of VK2809 in patients with hypercholesterolemia and fatty liver disease, which we expect to complete in 1H17."
Treatment with VK2809 was shown to be safe and well-tolerated at all doses studied in this trial. No serious adverse events were reported and no treatment- or dose-related trends were observed for abnormal vital signs, electrocardiograms, cardiac rhythm or physical examination assessments. Consistent with liver-targeted thyroid receptor activation, mild, asymptomatic elevations in liver enzymes and decreased thyroid hormone levels were observed at higher doses. Metabolically, VK2809 was not eliminated intact through the kidneys, and less than 3% of the administered dose was eliminated through the kidneys as the drug's active metabolite, VK2809A.
Viking previously announced top-line data from the Phase 1b trial which demonstrated clinically and statistically significant placebo-adjusted reductions in LDL-C ranging from 15.2% at the 5.0 mg dose (p=0.026) to 41.2% at the 20 mg dose (p<0.0001). In addition, subjects experienced placebo-adjusted reductions in triglycerides ranging from 34.8% at 5.0 mg dose (p=0.052) to 78.6% at the 40 mg dose (p=0.0001).
The company recently initiated a Phase 2 clinical trial of VK2809 in patients with primary hypercholesterolemia and non-alcoholic fatty liver disease. The Phase 2 clinical trial is a randomized, double-blind, placebo-controlled, parallel group study designed to evaluate the efficacy, safety and tolerability of VK2809 in approximately 80 patients with elevated LDL-C and non-alcoholic fatty liver disease.
1Mayo Clinic Proceedings, November 2013; 88(11): 1294-1311.
2J. Intern. Med., March 2006; 259(3): 247-258.
VK2809 is an orally available, tissue and receptor-subtype selective agonist of the thyroid beta receptor in Phase 2 development for the treatment of patients with hypercholesterolemia and fatty liver disease. VK2809 belongs to a family of novel prodrugs which are cleaved in vivo to release potent thyromimetics. Selective activation of the TRß receptor in liver tissue is believed to favorably affect cholesterol and lipoprotein levels via multiple mechanisms, including increasing the expression of low-density lipoprotein (LDL) receptors and increasing mitochondrial fatty acid oxidation.
In a Phase 1b study in patients with mild hypercholesterolemia, treatment with VK2809 resulted in placebo-adjusted reductions in low-density lipoprotein that exceeded 40% at high doses. Patients also experienced significant reductions in triglycerides, as well as the atherogenic proteins lipoprotein-a and apolipoprotein B. Consistent with its liver- and receptor-selective mechanism of action, treatment with VK2809 has also demonstrated rapid reduction of liver fat in animal models of hepatic steatosis. Further animal data have shown that VK2809 has additive cholesterol lowering activity in combination with statins. These characteristics suggest a highly differentiated therapeutic profile relative to existing oral options for patients with hypercholesterolemia and fatty liver disease, such as nonalcoholic steatohepatitis (NASH). The potential markets for these indications are significant. In the U.S., approximately 33% of adults, or 71 million people, have elevated LDL cholesterol. Additionally, NASH is becoming recognized as a leading cause of cirrhosis and liver failure and affects an estimated 6 to 15 million Americans.
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.
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. 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; 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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