VK0214 is an experimental oral treatment being developed by Viking Therapeutics to treat adrenoleukodystrophy (ALD). Research indicates that VK0214 positively impacts key genes and biomarkers that may affect the onset of ALD, also known as X-linked adrenoleukodystrophy (X-ALD).
How does VK0214 work?
ALD is a rare, genetic metabolic disorder characterized by the accumulation of molecules called very long-chain fatty acids (VLCFAs) inside cells. A buildup of VLCFAs is toxic for cells.
Mutations in the ABCD1 gene cause ALD. This gene contains the instructions for cells to make the adrenoleukodystrophy protein (ALDP) that is necessary to transport VLCFAs into a portion of the cell called peroxisomes. Peroxisomes then breakdown the VLCFAs so that cells can reuse the pieces to form new molecules. Mutations in the ABCD1 gene result in reduced or missing levels of ALDP, which causes the buildup of VLCFAs.
VK0214 is a small molecule that binds to and activates the thyroid beta receptor (TBR), which controls the activity of another gene called ABCD2. This gene produces the ABCD2 protein that plays a similar role to ALDP in the transport of VLCFAs into peroxisomes. By activating TBRs, researchers think that VK0214 could reduce the amount of VLCFAs in the body.
VK0214 in clinical trials
Researchers investigated VK0214 in preclinical studies in a mouse model of ALD. Mice that received VK0124 orally for 25 weeks (roughly six months) showed significantly reduced VLCFA levels in the blood, liver, and central nervous system (brain and spinal cord) compared with control mice. The treatment also increased the levels of the ABCD2 protein by 35% in the brain and 262% in the liver compared with the control animals. These results support the proposed mechanism that VK0214 increases ABCD2 levels, ultimately resulting in a decrease in VLCFAs.
Based on these preclinical findings, Viking is initiating a Phase 1 clinical trial in healthy participants. The trial will investigate the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) in order to determine the optimal dose of treatment. With SAD, each participant receives a single dose but each group of patients receives a higher dose. Conversely, with MAD, each patient receives multiple doses with increasing doses for each new group.
Participants will be randomly assigned to receive either the oral dose of VK0214 or a matching placebo during the trial. The trial also will investigate the pharmacokinetics, or movement in the body, of VK0214.
Once researchers determine the optimal dose parameters, they plan to initiate a Phase 1b study in patients with ALD.
The U.S. Food and Drug Administration granted VK0214 orphan drug designation in 2016. That special status is given to a medication designed to to treat a rare disease and provides development incentives, including tax credits.
Last updated: Dec. 8, 2020
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