Viking Therapeutics, a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, announced positive top-line results from a 12-week Phase 2 study of VK2809, its novel liver-selective thyroid receptor beta agonist, in patients with non-alcoholic fatty liver disease (NAFLD) and elevated low-density lipoprotein cholesterol (LDL-C). The study successfully achieved its primary endpoint, with patients receiving VK2809 demonstrating statistically significant reductions in LDL-C compared with placebo.
In addition, the trial’s secondary endpoint was achieved, with VK2809-treated patients experiencing statistically significant reductions in liver fat content compared with placebo. An abstract describing the results has been submitted for consideration for presentation at The Liver Meeting 2018, the annual meeting of the American Association for the Study of Liver Diseases (AASLD), scheduled for November 9-13, 2018 in San Francisco, CA.
Reduction in LDL-C
Patients receiving VK2809 demonstrated statistically significant reductions in LDL-C of 20% or more, compared with placebo-treated patients. In addition, VK2809-treated patients demonstrated statistically significant improvements in other lipids, including atherogenic proteins apolipoprotein B and lipoprotein (a).
Reduction in Liver Fat Content
Patients receiving VK2809 experienced statistically significant reductions in liver fat content, as assessed by magnetic resonance imaging, proton density fat fraction (MRI-PDFF), relative to placebo after 12 weeks of treatment.
“This proof-of-concept study demonstrates robust improvement in liver fat by VK2809 versus placebo. The trial utilized a state-of-the-art method, MRI-PDFF, as a non-invasive quantitative biomarker of changes in liver fat content. Previous studies by our group have shown that a 30 percent or greater reduction in MRI-PDFF is associated with higher odds of histologic response in NASH. The quantum of liver fat reduction along with LDL-lowering properties of VK2809 are potentially likely to be beneficial in patients with non-alcoholic steatohepatitis (NASH) who have a significant risk of not only liver fibrosis progression but also cardiovascular disease,” stated Rohit Loomba, MD, MHSc, director, NAFLD research center, and professor of medicine, University of California at San Diego.
Safety and Tolerability
No serious adverse events (SAEs) were reported among patients receiving VK2809 or placebo. Mean alanine aminotransferase (ALT) levels among patients receiving VK2809 were reduced from baseline relative to those of patients receiving placebo. Among patients with elevated baseline ALT levels, those receiving VK2809 also demonstrated reduction relative to placebo. There were no clinically or numerically meaningful differences in direct bilirubin, indirect bilirubin, alkaline phosphatase, or international normalized ration (INR) between patients treated with VK2809 or placebo.
In addition, no meaningful changes to the thyroid hormone axis were observed among VK2809-treated patients compared with placebo-treated patients.
VK2809 was also shown to be well-tolerated in this study. Gastrointestinal-related side effects such as diarrhea and nausea were numerically higher in placebo-treated patients relative to VK2809-treated cohorts. Further data on safety and tolerability from this study will be submitted for presentation at an upcoming medical conference.
“We are encouraged by the preliminary efficacy and safety profile VK2809 has shown in this study,” stated Brian Lian, Ph.D., chief executive officer of Viking. “VK2809’s effect on liver fat at 12 weeks appears to exceed all other oral agents currently in development for NASH, supporting our view that VK2809 has a best-in-class profile. Based on published data from multiple studies, we anticipate that these liver fat reductions would result in longer-term histologic benefit. In addition, the improvement in lipid parameters observed in this study suggests potential benefits in cardiovascular health, an important consideration in this population. We look forward to pursuing further development of VK2809 in NASH.”
The Phase 2 study was a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of VK2809 in patients with elevated LDL-C and NAFLD. Patients were randomized to receive placebo (n = 14), 10 mg VK2809 dosed every other day (QOD, n = 15), or 10 mg VK2809 dosed daily (QD, n = 16) for 12 weeks followed by a four-week off-drug phase.
The trial’s primary endpoint assessed the effect of VK2809 treatment on LDL-C after 12 weeks compared to placebo. The secondary endpoint evaluated changes in liver fat content by MRI-PDFF in patients with a valid baseline and post-baseline MRI.
(Source: Viking Therapeutics, Inc.)
Filed Under: Drug Discovery and Development