Viking Therapeutics Announces Results from Phase 1b Clinical Trial of VK0214 in Patients with X-ALD

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Oct 09, 2024, 07:00 ET

Reductions in Very Long-Chain Fatty Acids and Plasma Lipid Levels Observed After 28 Days of Once Daily Dosing

VK0214 Shown to be Safe and Well-Tolerated in 28-Day Study

SAN DIEGO, Oct. 9, 2024 /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 positive data from the company's 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). Results from this study showed VK0214 to be safe and well-tolerated following once-daily dosing over the 28-day study period. In addition, significant reductions were observed in plasma levels of very long-chain fatty acids (VLCFAs) and other lipids, as compared to placebo.

Highlights from the study results include:

Reductions in VLCFAs

In addition to safety and tolerability, the study included an exploratory assessment of changes in plasma levels of VLCFAs after 28 days of dosing. VLCFAs are considered biomarkers of disease in patients with X-ALD. Treatment with VK0214 resulted in significant reductions in mean VLCFA levels at both doses evaluated, 20 mg/day and 40 mg/day, compared to placebo. Importantly, cohorts receiving VK0214 demonstrated reductions in mean plasma levels of the 26 carbon lysophosphatidyl choline (C26:0-LPC) derivative, a key diagnostic marker.

Percent Change from Baseline in VLCFAs Following 28 Days of Treatment of VK0214

	Placebo¹ (n=6)	20 mg (n=8)	40 mg (n=9)
C22:0	4.0 %	-16.6 %	-19.5 %
p-value vs. placebo²	-	0.0097	0.0042
C24:0	5.2 %	-12.8 %	-18.0 %
p-value vs. placebo	-	0.0162	0.0029
C26:0	20.8 %	-17.4 %	-17.6 %
p-value vs. placebo	-	0.0145	0.0117
C26:0-LPC³	23.1 %	-8.4 %	-14.8 %
p-value vs. placebo	-	0.0427	0.0105

Notes: 1) Least squares mean change from baseline to Day 28. 2) Two-sided t-test using mixed model for repeated measures. 3) C26:0-LPC data for 20 mg, 40 mg cohorts include results from n=7, n=8 subjects, respectively.

Reductions in Plasma Lipids

In addition to VLCFA changes, subjects who received VK0214 demonstrated reductions in other plasma lipids. Mean reductions relative to baseline and placebo were observed for low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) [Lp(a)] following 28 days of treatment.

Percent Change in Lipid Markers Following 28 Days of Treatment of VK0214

	Placebo¹ (n=6)	20 mg (n=9)	40 mg (n=9)
LDL-C	4.7 %	-19.4 %	-20.2 %
p-value vs. placebo²	-	<0.0001	<0.0001
ApoB	8.6 %	-16.3 %	-22.0 %
p-value vs. placebo	-	0.0004	<0.0001
Lp(a)	17.5 %	-22.1 %	-26.8 %
p-value vs. placebo	-	0.0199	0.0105

Notes: 1) Least squares mean change from baseline to Day 28. 2) Two-sided t-test using mixed model for repeated measures.

Safety and Tolerability

VK0214 demonstrated encouraging safety and tolerability following 28 days of once-daily dosing. Treatment emergent adverse events were reported as mild to moderate; one subject in the placebo cohort experienced a wrist fracture that was characterized as a severe adverse event. Gastrointestinal adverse events were slightly higher among placebo subjects (33%) compared with VK0214-treated subjects (11%).

"We are excited to report these initial results evaluating VK0214 in patients with adrenomyeloneuropathy," said Brian Lian, Ph.D., chief executive officer of Viking. "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. We look forward to exploring next steps with this important compound."

The Phase 1b trial was a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with the adrenomyeloneuropathy (AMN) form of X-ALD. The study enrolled patients across three cohorts: placebo, VK0214 20 mg daily, and VK0214 40 mg daily. The primary objectives were to evaluate the safety and tolerability of VK0214 in subjects with AMN, when administered once-daily over a 28-day dosing period. Secondary objectives included an evaluation of the pharmacokinetics of VK0214 following 28 days of dosing in this population. An exploratory objective was to evaluate the effects of VK0214 on plasma levels of VLCFAs in subjects with AMN.

About X-ALD
X-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. In X-ALD, mutations in a gene known as ABCD1 lead to dysfunction of the adrenoleukodystrophy protein (ALDP), an important peroxisomal transporter. In patients, this dysfunction leads to an accumulation of VLCFAs, which can trigger a rapid, inflammatory demyelination, resulting in cognitive impairment, motor skill deterioration, and even death. Research in disease models has shown that increasing the expression of a related gene known as ABCD2, which encodes a compensatory transporter called the adrenoleukodystrophy related protein (ADLRP), can result in normalization of VLCFA levels. Activation of the thyroid hormone beta receptor, as observed in patients treated with VK0214, has been shown to increase the expression of ABCD2 resulting in reductions in VLCFA levels. X-ALD is estimated to occur in approximately 1 in 17,000 births. Currently there are no pharmacologic treatments approved for the disease.

About Viking Therapeutics, Inc.
Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. Viking'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. The compound successfully achieved both the primary and secondary endpoints in a recently completed Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a 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. Viking is also developing VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 and a Phase 2 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. The company is also evaluating an oral formulation of VK2735 in a Phase 1 trial. In the rare disease space, Viking is 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 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD.

For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com.

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 clinical and preclinical development programs, anticipated timing for reporting clinical data and cash resources. 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 VK2735, VK0214, VK2809, the company's incretin receptor agonists, and its amylin and calcitonin receptor agonists; risks that prior clinical and preclinical results may not be replicated; risks regarding regulatory requirements; 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, 2023, 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.

SOURCE Viking Therapeutics, Inc.