Viking Therapeutics Reports Phase 1b Trial Results of VK0214 in X-ALD Patients

In an announcement on October 9, 2024, Viking Therapeutics, Inc. reported promising findings from its Phase 1b clinical trial of VK0214, a novel small molecule agonist of the thyroid hormone receptor beta (TRβ), in patients with X-linked adrenoleukodystrophy (X-ALD). This study revealed that VK0214 was safe and well-tolerated with once-daily dosing over a 28-day period. The therapy also led to significant reductions in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids compared to placebo, demonstrating potential therapeutic benefits.

Key highlights from the study include notable reductions in VLCFAs, which are biomarkers of the disease in X-ALD patients. Participants treated with VK0214 experienced significant decreases in mean VLCFA levels at both evaluated doses, 20 mg/day and 40 mg/day, in contrast to those receiving a placebo. Of particular importance, there were reductions in mean plasma levels of the 26 carbon lysophosphatidyl choline (C26:0-LPC) derivative, a crucial diagnostic marker for X-ALD.

Additionally, subjects treated with VK0214 showed reductions in other plasma lipids, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)]. These reductions were observed in comparison to baseline levels and placebo, suggesting broader benefits for overall cardiometabolic health.

The safety and tolerability of VK0214 were encouraging. Adverse events related to the treatment were mild to moderate, with a slightly higher incidence of gastrointestinal issues among placebo subjects (33%) compared to those treated with VK0214 (11%). One severe adverse event, a wrist fracture, was reported in the placebo cohort.

“We are thrilled to share these initial findings on VK0214 in patients with adrenomyeloneuropathy,” said Brian Lian, Ph.D., CEO of Viking Therapeutics. He noted that patients receiving VK0214 showed progressive improvements in plasma levels of very long-chain fatty acids within the brief treatment period. Furthermore, VK0214 continued to exhibit benefits on broader plasma lipids, reinforcing its potential for enhancing overall cardiometabolic health. Consistent with prior clinical results in healthy volunteers, VK0214 was proven safe and well-tolerated in this 28-day study. Dr. Lian expressed anticipation for further exploration of this compound.

The Phase 1b trial was a multi-center, randomized, double-blind, placebo-controlled study involving adult male patients with the adrenomyeloneuropathy (AMN) form of X-ALD. Participants were divided into three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily. The primary goals were to assess the safety and tolerability of VK0214 when administered once daily over 28 days. Secondary objectives included evaluating the pharmacokinetics of VK0214, while an exploratory objective aimed to examine the effects of VK0214 on plasma levels of VLCFAs in subjects with AMN.

X-ALD is a rare and often fatal metabolic disorder characterized by demyelination, or the breakdown of protective barriers around brain and nerve cells. Mutations in the ABCD1 gene cause dysfunction in the adrenoleukodystrophy protein (ALDP), leading to an accumulation of VLCFAs, which can trigger rapid and inflammatory demyelination, resulting in cognitive impairment, motor skill deterioration, and potentially death. Research suggests that increasing the expression of the ABCD2 gene, which encodes a compensatory transporter, can normalize VLCFA levels. Activating the thyroid hormone beta receptor, as seen with VK0214 treatment, has been shown to increase ABCD2 expression, thereby reducing VLCFA levels. X-ALD occurs in approximately 1 in 17,000 births, and there are currently no approved pharmacologic treatments for the disease.

Viking Therapeutics is dedicated to developing novel therapies for metabolic and endocrine disorders. The company is advancing several compounds, including VK2809 for lipid and metabolic disorders and VK2735 for various metabolic conditions. Viking continues to evaluate the potential of VK0214 as a treatment for X-ALD, based on the promising results from this recent study.