Viking Therapeutics Announces Results from Phase 1 Clinical Trial of Novel Oral Thyroid Receptor Beta Agonist VK0214

First-in-Human Clinical Trial of Novel, Selective Thyroid Receptor Beta Agonist Demonstrates Encouraging Safety and Tolerability; Predictable Pharmacokinetics Statistically Significant Reductions Observed for Key Lipids, Including LDL Cholesterol, Triglycerides and Apolipoprotein B Phase 1b Study in X-ALD Patients to be Initiated in Coming Weeks

June 17, 2021 7:05 AM EDT

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SAN DIEGO, June 17, 2021 /PRNewswire/ -- Viking Therapeutics, Inc. (Viking) (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced results from the company's Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) clinical trial of VK0214, a novel, orally available small molecule thyroid receptor beta (TRβ) agonist in development for the potential treatment for X-linked adrenoleukodystrophy (X-ALD).  In this study, VK0214 demonstrated encouraging safety and tolerability, as well as a predictable pharmacokinetic (PK) profile.  The company expects to initiate a Phase 1b study of VK0214 in patients with X-ALD in the coming weeks.

The Phase 1 trial was a randomized, double-blind, placebo-controlled study in healthy volunteers.  The primary objective of the study was to evaluate the safety and tolerability of VK0214 administered orally for up to 14 days.  The secondary objective was to evaluate the pharmacokinetics of VK0214 following single and multiple oral doses.  The first portion of the study evaluated single doses of VK0214; in the second portion of the study subjects received VK0214 once daily for 14 days.  Subsequent cohorts in both parts of the study received successively higher VK0214 doses.

VK0214 was shown to be safe and well-tolerated at all doses evaluated in this study.  No serious adverse events were reported, and no treatment or dose-related trends were observed for vital signs, gastrointestinal effects, cardiovascular measures, or physical examinations.  VK0214 demonstrated dose-dependent exposures, no evidence of accumulation following multiple doses, and a half-life consistent with anticipated once-daily dosing regimens.

While the study's primary objective was to evaluate safety and tolerability, laboratory assessments included a lipid panel to determine potential pharmacodynamic effects following exposure to VK0214.  The results showed that subjects who received VK0214 experienced reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and apolipoprotein B following 14 days of treatment at all VK0214 doses.  Many of the observed lipid reductions achieved statistical significance, though the study was not powered to demonstrate statistical significance on laboratory assessments. 

% Change in Lipid Markers Following 14 Days of Treatment of VK0214



5 mg


10 mg


25 mg


50 mg


75 mg


100 mg


























(1) Excludes one placebo subject due to an anomalous triglyceride value (>7x higher than SD). *p

In addition to general lipid assessments, an evaluation of very long chain fatty acids (VLCFAs) was also performed.  Despite relatively low baseline levels and the presence of a functional ABCD1 gene in these healthy volunteers, treatment with VK0214 produced reductions in VLCFA levels at all doses above 5 mg.  Numerical improvements in excess of 20% from baseline were observed for multiple VLCFAs, including the key C26:0 VLCFA marker that is often elevated in patients with X-ALD, compared with a mean increase of 2.6% in placebo subjects.  The VLCFA-reducing activity of VK0214 may provide benefit in a population of X-ALD patients, who by nature have high levels of accumulated VLCFAs due to pathogenic mutations in the ABCD1 gene.

"We are encouraged by the overall safety and tolerability displayed by VK0214 in this study, along with the compound's predictable pharmacokinetic profile," said Brian Lian, Ph.D., chief executive officer of Viking Therapeutics.  "Additionally, we were pleased to see significant reductions in key lipids such as LDL-C and triglycerides, which suggest therapeutic activity that is similar to our other clinical-stage thyroid hormone receptor beta agonist, VK2809.  We look forward to evaluating VK0214 in X-ALD patients in our planned Phase 1b study and expect to have this trial underway shortly."

Activation of the thyroid beta receptor has been shown to affect the expression of genes that are relevant to the manifestation of X-ALD.  In X-ALD, mutations in the ABCD1 gene lead to dysfunction of the adrenoleukodystrophy protein (ALDP), an important peroxisomal transporter.  In patients, this dysfunction leads to an accumulation of VLCFAs, which is believed to contribute to the onset and progression of the disease. Research in disease models has shown that increasing the expression of a related gene called ABCD2, which encodes a compensatory transporter called the adrenoleukodystrophy related protein (ADLRP), can result in normalization of VLCFA levels.

In preclinical studies, VK0214 has been shown to potently activate the thyroid beta receptor, a regulator of ABCD2 gene expression, leading to increased expression of ABCD2. Data from in vivo studies have demonstrated that administration of VK0214 produces a significant reduction of VLCFAs in both plasma and tissue, potentially leading to a therapeutic benefit. VK0214 has been granted orphan drug designation by the FDA for the treatment of X-ALD. 

About X-ALDX-ALD is a rare and often fatal metabolic disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells; a process known as demyelination. The disease, for which there is no approved treatment, is caused by mutations in a peroxisomal transporter of VLCFAs, known as ABCD1. As a result, transporter function is impaired, and patients are unable to efficiently metabolize VLCFAs. The resulting accumulation can trigger a rapid, inflammatory demyelination, which leads to cognitive impairment, motor skill deterioration, and even death. X-ALD is estimated to occur in approximately 1 in 17,000 births.

The thyroid beta receptor is known to regulate expression of an alternative VLCFA transporter, known as ABCD2. Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism.

About Viking Therapeutics, Inc.

Viking Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel, orally available, first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders.  Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives.  The company's clinical programs include VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders, which is currently being evaluated in a Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis.  In a Phase 2 trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo.  The company is also developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD).  VK0214 is currently being evaluated in a Phase 1 first-in-human clinical trial.  The company holds exclusive worldwide rights to a portfolio of five therapeutic programs, including those noted above, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.

For more information about Viking Therapeutics, please visit Follow Viking on Twitter @Viking_VKTX.

Forward-Looking Statements

This press release contains forward-looking statements regarding Viking Therapeutics, Inc., under the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995, including statements about Viking's expectations regarding its development activities and plans regarding VK0214 and its prospects and the timing for commencing Viking's Phase 1b study of VK0214 in patients with X-ALD. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially and adversely and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: risks associated with the success, cost and timing of Viking's product candidate development activities and clinical trials, including those for VK2809 and VK0214; risks that prior clinical and preclinical results may not be replicated; risks regarding regulatory requirements; risks related to the COVID-19 pandemic; and other risks that are described in Viking's most recent periodic reports filed with the Securities and Exchange Commission, including Viking's Annual Report on Form 10-K for the year ended December 31, 2020, and subsequent Quarterly Reports on Form 10-Q, including the risk factors set forth in those filings. These forward-looking statements speak only as of the date hereof.  Viking disclaims any obligation to update these forward-looking statements except as required by law.


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SOURCE Viking Therapeutics, Inc.

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