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
|
|
|
Placebo1
(n=11)
|
5
mg
(n=6)
|
10
mg
(n=6)
|
25
mg
(n=6)
|
50
mg
(n=6)
|
75
mg
(n=6)
|
100
mg
(n=6)
|
|
|
|
|
|
|
|
|
LDL-C
|
3.8%
|
-0.7%
|
-12.5%*
|
-21.4%**
|
-19.5%**
|
-19.1%***
|
-18.9%**
|
|
|
|
|
|
|
|
|
Triglycerides
|
4.9%
|
-6.7%
|
-19.5%*
|
-1.7%
|
-36.8%**
|
-45.0%***
|
-39.1%**
|
|
|
|
|
|
|
|
|
ApoB
|
4.4%
|
-5.7%
|
-12.5%**
|
-23.3%***
|
-24.0%***
|
-28.3%***
|
-28.2%***
|
(1) Excludes one
placebo subject due to an anomalous triglyceride value (>7x
higher than SD). *p < 0.05; **p < 0.01; ***p <
0.001.
|
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-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. 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
www.vikingtherapeutics.com. 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.