Viking Therapeutics has announced positive results from its Phase 1b clinical trial of VK0214, a thyroid hormone receptor beta agonist, in patients with X-linked adrenoleukodystrophy (X-ALD). The multicenter, double-blind, randomized, placebo-controlled trial assessed the safety, tolerability, and pharmacokinetics of VK0214 when administered once daily over 28 days to adult male patients with the adrenomyeloneuropathy (AMN) form of X-ALD across three cohorts.
The primary objectives of the trial were to evaluate the safety and tolerability of VK0214. Secondary objectives included assessing the pharmacokinetics of the drug after 28 days of dosing. An exploratory objective was to determine VK0214’s effects on plasma levels of very long-chain fatty acids (VLCFAs), which serve as biomarkers for X-ALD.
Significant Reduction in VLCFAs
Trial results indicated that VK0214 was safe and well-tolerated following the dosing period. Significant reductions in plasma levels of VLCFAs were observed, as well as other lipids, when compared to the placebo. Both the 20 mg/day and 40 mg/day doses of VK0214 led to significant decreases in mean VLCFA levels, including the 26 carbon lysophosphatidyl choline (C26:0-LPC) derivative – a key diagnostic marker for X-ALD. A 14.8% reduction was observed in the 40 mg cohort (p=0.0105) and a reduction of 8.4% in the 20 mg cohort (p=0.0427).
Improvements in Plasma Lipids
Subjects receiving VK0214 demonstrated reductions in other plasma lipids, including low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] following 28 days of treatment. These results were relative to both baseline and placebo. Treatment-emergent adverse events were found to be mostly mild to moderate, with one severe adverse event – a wrist fracture – reported in the placebo cohort.
Analyst Perspective
William Blair highlights that the positive progress of VK0214 provides investors with additional opportunities beyond Viking's existing programs, including the subcutaneous and oral formulations of VK2735 for obesity, VK2809 for metabolic-dysfunction-associated steatohepatitis (MASH), and its preclinical amylin program, which is expected to enter clinical trials next year. The analyst believes that the focus on treating an orphan disease broadens Viking's potential revenue streams by expanding from the larger obesity and MASH markets into the rare disease space.
Company Statement
Viking Therapeutics CEO Brian Lian stated, “Patients receiving VK0214 demonstrated progressive improvement in plasma levels of very long chain fatty acids in the relatively brief treatment period evaluated in this study. In addition, VK0214 continued to show benefits on broader plasma lipids, such as LDL-C, important for overall cardiometabolic health. Consistent with prior clinical results in healthy volunteers, VK0214 was shown to be safe and well-tolerated in this 28-day study.”
