SAN DIEGO, Oct. 4, 2017 /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 top-line results
from a 25-week proof-of-concept study of VK0214 in an in
vivo model of X-linked adrenoleukodystrophy (X-ALD). The
results of this study showed that VK0214 led to statistically
significant reductions in plasma levels of multiple very long chain
fatty acids (VLCFAs) in treated animals compared with vehicle
controls. Additionally, VK0214-treated animals demonstrated
statistically significant reductions in VLCFA levels within key
tissues, including liver, brain and spinal cord. As the
accumulation of VLCFAs is believed to contribute to the underlying
pathology of X-ALD, these data provide additional support for the
continued evaluation of VK0214 in this indication.
The results showed that 25 weeks of treatment with VK0214 led to
robust effects on multiple VLCFAs, including statistically
significant reductions in plasma levels of saturated C26, C24, C22,
and C20 fatty acids ranging from 45% to 82% relative to controls.
Importantly, these reductions were generally maintained or
increased in magnitude over the course of the 25-week study,
suggesting a potentially progressive and durable effect. These
data compare favorably to results from a prior six-week study, with
improvements observed on all key VLCFA measures relative to the
prior study. These results further support the thesis that
activation of the thyroid beta receptor can lead to an improved
metabolic profile in this setting.
The study also evaluated the effect of VK0214 on VLCFA levels in
various tissues. After 25 weeks of treatment, VK0214 was
shown to reduce levels of VLCFAs in liver, brain and spinal cord.
This suggests an added potential therapeutic benefit, as
elevated tissue VLCFA levels may contribute to the underlying
cerebral and myelotoxicities observed in X-ALD. Detailed
results will be presented at the upcoming 87th Annual
Meeting of the American Thyroid Association, October 18-22 in Victoria, British Columbia.
"This is the second study in which we have generated encouraging
evidence of the therapeutic potential of VK0214 in this
debilitating disease. The impressive effects on plasma VLCFAs
strengthen our belief that activation of the thyroid beta receptor
can lead to improved lipid processing. The reduction in
tissue VLCFAs is particularly exciting, as it suggests a potential
direct benefit on tissue-related toxicities," said Brian Lian, Ph.D., chief executive officer of
Viking. "Importantly, these longer-term results demonstrate
improved pharmacologic effects relative to the prior six-week
study, with no evidence of safety or tolerability issues. We
look forward to continuing our evaluation of VK0214 in this
setting."
The 25-week proof-of-concept study, conducted at the Kennedy
Krieger Institute under a sponsored research agreement with Viking,
was designed to evaluate changes in VLCFA levels in the ABCD1
knockout mouse model. This model is intended to mirror the
loss of ABCD1 transporter activity that is considered the hallmark
of X-ALD. Mice received VK0214 or vehicle daily for 25
weeks. Plasma VLCFA levels were determined by measuring
unsaturated lysophosphatidylcholine fatty acid esters, which are
biomarkers for VLCFAs in X-ALD. Additional work is underway
to better understand VK0214's therapeutic effect in models of this
disease, including an elucidation of anti-inflammatory properties
that have been observed in preliminary studies in human
macrophages.
About VK0214
VK0214 has been granted orphan drug
status by the U.S. Food and Drug Administration for the treatment
of X-linked adrenoleukodystrophy. The molecule is a novel,
orally available thyroid receptor beta (TRβ) agonist that
selectively modulates lipoprotein and triglyceride levels in liver
tissue. This mechanism has been demonstrated to affect the
expression of the genes that are relevant to the manifestation of
X-ALD. In X-ALD, mutations in the ABCD1 gene lead to the
accumulation of very long-chain fatty acids (VLCFAs) which is
believed to be a fundamental cause of the disease. Research
has shown that increasing the expression of the ABCD2 gene can
counteract this process and lead to normalization of VLCFA
levels. In preclinical studies, VK0214 has been shown to
induce expression of ABCD2 by increasing TRβ activity, leading to
the belief that it may provide therapeutic benefit to X-ALD
patients.
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
VLCFA. 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,
Inc. is a clinical-stage biopharmaceutical company focused on the
development of novel, first-in-class or best-in-class therapies for
metabolic and endocrine disorders. The company's research and
development activities leverage its expertise in metabolism to
develop innovative therapeutics designed to improve patients'
lives. Viking has exclusive worldwide rights to a portfolio
of five therapeutic programs in clinical trials or preclinical
studies, which are based on small molecules licensed from Ligand
Pharmaceuticals Incorporated. The company's clinical programs
include VK5211, an orally available, non-steroidal selective
androgen receptor modulator, or SARM, in Phase 2 development for
the treatment and prevention of lean body mass loss in patients who
have undergone hip fracture surgery, VK2809, a small molecule
thyroid beta agonist in Phase 2 development for
hypercholesterolemia and fatty liver disease, and VK0612, a
first-in-class, orally available drug candidate in Phase 2
development for type 2 diabetes. Viking is also developing
novel and selective agonists of the thyroid beta receptor for GSD
Ia and X-linked adrenoleukodystrophy, as well as two earlier-stage
programs targeting metabolic diseases and anemia.
Follow Viking on Twitter @Viking_VKTX.
Forward-Looking Statements
This press release
contains forward-looking statements regarding Viking Therapeutics,
including statements about Viking's expectations regarding its
development activities, timelines and milestones, as well as the
company's goals and plans regarding VK0214 and VK0214's prospects.
Forward-looking statements are subject to risks and uncertainties
that could cause actual results to differ materially 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 VK5211 and VK2809; risks that prior
clinical and pre-clinical results, including those for VK0214, may
not be replicated; and risks regarding regulatory requirements,
among others. These forward-looking statements speak only as of the
date hereof. Viking disclaims any obligation to update these
forward-looking statements.
View original
content:http://www.prnewswire.com/news-releases/viking-therapeutics-announces-top-line-results-from-proof-of-concept-study-of-vk0214-in-in-vivo-model-of-x-linked-adrenoleukodystrophy-x-ald-300530670.html
SOURCE Viking Therapeutics, Inc.