SAN DIEGO, Oct. 23, 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 results from a 25-week proof-of-concept study of VK0214 in
an in vivo model of X-linked adrenoleukodystrophy
(X-ALD). The final study data were presented in a poster
presentation at the 87th Annual Meeting of the American
Thyroid Association (ATA), held October
18-22, 2017, in Victoria,
British Columbia.
The results of this study showed that treatment with VK0214 led
to statistically significant reductions in plasma levels of
multiple very long chain fatty acids (VLCFAs), including the
benchmark highly toxic C26 fatty acid, in treated animals compared
with vehicle controls. VLCFA levels in CNS tissues were also
significantly reduced, suggesting a potential direct benefit in
both 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 role of selective thyroid
receptor beta (TRb) activation as a potential therapeutic approach
to the disease.
Key results from the study included:
- Treatment with VK0214 produced robust and durable reductions in
plasma levels of the lysophosphatidylcholine (LPC) derived C26:0,
C24:0, C22:0 and C20:0 very long chain fatty acid esters throughout
the study.
-
- Plasma C26:0-LPC levels were reduced by up to 57% through the
course of the study, compared to vehicle controls (p < 0.005 at
week 6 and p < 0.0001 at weeks 9, 12, 20 and 25).
- Plasma C24:0-LPC levels were reduced by up to 61% compared to
vehicle controls (p < 0.0001).
- Plasma C22:0-LPC levels were reduced by up to 74% compared to
vehicle controls (p < 0.0001).
- Plasma C20:0-LPC levels were reduced by up to 82% compared to
vehicle controls (p < 0.0001).
- Importantly, the reductions in plasma VLCFAs were generally
maintained or increased in magnitude over the course of the 25-week
study, suggesting a potentially progressive and durable
effect.
- Treatment with VK0214 also led to significant reductions in
C26:0, C24:0, C22:0 and C20:0 VLCFA levels in brain, spinal cord
and liver tissue.
-
- Brain levels of C20:0-, C22:0-, and C26:0-LPC were reduced by
34%, 12%, and 11%, respectively (p < 0.001, p < 0.05, and p =
0.07, respectively).
- Spinal cord levels of C20:0 and C26:0 were reduced by 9%, and
15%, respectively (p < 0.05 for each).
- Liver levels of C20:0, C24:0, and C26:0 were reduced by 59%,
49% and 19%, respectively (p < 0.0001, p < 0.0001, and p <
0.05, respectively).
- Treatment with VK0214 stimulated significant increases in ABCD2
transporter expression, as assessed by quantitative polymerase
chain reaction (qPCR) analysis. Brain ABCD2 expression
increased by 35% (p < 0.05) and liver ABCD2 expression increased
by 262% (p < 0.05), compared with vehicle controls. These
increases are consistent with the proposed mechanism of
TRb-mediated reductions in VLCFA levels, as ABCD2 is regulated by
TRb and known to play a role in VLCFA metabolism.
"These results are particularly exciting as they demonstrate the
first evidence of VK0214's effects in CNS tissues," said
Brian Lian, Ph.D., chief executive
officer of Viking. "The observed reductions in brain and
spinal cord VLCFAs, combined with the stimulation of brain ABCD2
expression suggest potential benefits in tissues that are difficult
to penetrate and especially prone to degeneration in X-ALD.
In addition to the potent and durable reductions of plasma VLCFAs,
we believe these results provide compelling support for the
continued 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 oral 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.
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