Novel Thyroid Receptor Can Improve LDL-C, Liver Fat Content in NAFLD
VK2809, a novel liver-directed thyroid receptor beta agonist, can significantly reduce low-density lipoprotein (LDL) cholesterol and improve the liver fat content in patients with non-alcoholic fatty liver disease (NAFLD), according to a new study.
The findings were presented during a late-breaking session at The Liver Meeting, hosted by the American Association for the Study of Liver Diseases.
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In preclinical models, VK2809 demonstrated reduced cholesterol, liver fat content, and fibrosis. Further, a previous 14-day study demonstrated promising safety and tolerability among humans.
Dr Loomba, who is the founding director of the NAFLD Translational Research Unit at University of California, San Diego, and colleagues held a multicenter randomized phase 2a trial to evaluate the safety, tolerability, and efficacy of VK2809 in patients with both NAFLD and hypercholesterolemia.
The researchers randomly assigned each participant to either 10 mg of oral VK2809 every other day, 10 mg of oral VK2809 every day, or a placebo for 12 weeks. All participants had a liver fat content of 8% or more, LDL cholesterol of 110 mg/dL or higher, and triglycerides of 120 mg/dL or higher.
Results indicated that participants who had received VK2809 experienced reductions in LDL cholesterol of at least 20% compared with participants who received placebo. Those who received VK2809 also had significant reductions in liver fat content when compared with the placebo group.
The mean absolute change from baseline in liver fat content was 8.9% for individuals who received VK2809 every other day and 10.6% for those who received VK2809 every day, whereas participants in the placebo group experienced a minimal change of 0.9%.
The median relative change from baseline in liver fat content was 56.5% for individuals who received VK2809 every other day, 59.7% for those who received VK2809 every day, and 8.9% for placebo.
Participants who took VK2809 were also more likely to have a reduction in magnetic resonance imaging, proton density fat fraction by 30% or more—76.9% for those who received VK2809 every other day, 90.9% for those who received VK2809 every day, and 18.2% for placebo.
“These data provide justification for further development of VK2809 as a potential treatment for patients with biopsy-proven NASH with fibrosis,” the researchers concluded.
—Colleen Murphy
Reference:
Loomba R, Neutel J, Bernard D, et al. LB-4 VK2809, a novel liver-directed thyroid receptor beta agonist, significantly reduces liver fat in patients with non-alcoholic fatty liver disease: a phase 2 randomized, placebo-controlled trial. Paper presented at: AASLD’s The Liver Meeting; November 9-13, 2018; San Francisco, CA. https://plan.core-apps.com/tristar_aasld18/abstract/1cd464b79336d9176dd9c2472ad33ec7. Accessed November 12, 2018.