SAN DIEGO, Sept. 7, 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
the presentation of positive final results from a proof-of-concept
study of VK2809 in an in vivo model of glycogen storage
disease type Ia (GSD Ia). GSD Ia is a rare, orphan genetic
disease that results in excess accumulation of glycogen and lipids
in liver tissue. The study results demonstrated that
treatment with VK2809 produced statistically significant reductions
in liver triglyceride content and liver weight compared with
vehicle-treated controls. Final results from the study were
summarized in a poster titled, "Evaluation of the Thyroid Hormone
Agonist VK2809 in an In Vivo Model of Glycogen Storage
Disease Type Ia," presented today at the 13th
International Congress of Inborn Errors of Metabolism (ICIEM), in
Rio De Janeiro, Brazil.
In this study, treatment with VK2809 led to statistically
significant reductions in key metabolic markers of GSD Ia after
just four days, highlighting the molecule's potent, rapid-acting
effect in liver tissue. Researchers utilized the
glucose-6-phosphatase (G6PC) knockout mouse model, which is
intended to replicate the impairment of this enzyme's activity in
patients with GSD Ia. Highlights of the data presented today
include:
- Mean total liver triglycerides were reduced by 69.0% in
VK2809-treated animals relative to vehicle-treated control animals
(p < 0.0001). Total liver triglyceride content in
VK2809-treated animals was reduced to within the range of the
study's wild type control mice (e.g. mice that did not possess the
genetic signature of GSD Ia).
- Mean liver weights were reduced by 35.7% in
VK2809-treated animals as compared to controls (p < 0.05).
Liver weights in treated animals were reduced to within the range
of wild type controls.
- Mean liver triglyceride concentration was reduced by
54.0% (p = 0.07).
In addition, liver mass as a percent of body mass was
significantly reduced among treated animals compared with controls
(p < 0.05), in line with the expected benefit of VK2809.
Additional evaluation of VK2809 on markers of autophagy and genes
associated with lipid metabolism in this model is ongoing.
"The data presented at ICIEM confirm and expand upon the initial
findings from this study which we reported earlier this year.
The rapid observed reductions in total liver triglyceride content
resulting from treatment with VK2809 suggest an encouraging
potential profile for patients who experience complications of GSD
Ia, such as hepatic steatosis. Total liver triglycerides in
VK2809-treated animals were reduced to within the range observed in
normal mice, demonstrating VK2809's ability to potentially
alleviate certain abnormalities associated with poor metabolic
control," said Brian Lian, Ph.D.,
chief executive officer of Viking. "These findings support
our plan to file an IND later this year to advance VK2809 into a
proof-of-concept study in patients with GSD Ia. We believe
VK2809's novel liver-targeting mechanism, combined with prior data
showing robust effects on plasma triglycerides in humans, represent
a potential approach to improving steatosis and metabolic control
in patients with GSD Ia. In addition, our recent data
demonstrating anti-fibrotic benefits from VK2809 may be relevant to
other glycogen storage diseases and we plan to further explore
potential applications in these settings."
GSD Ia is characterized by an inability to metabolize glucose
precursors, resulting in hypoglycemia and increased
lipogenesis. The disease is caused by mutations in the gene
for G6PC, a critical enzyme involved in the production of glucose
from either glycogen or gluconeogenesis. Impaired G6PC
function leads to dramatically elevated liver triglyceride levels
in human patients and in animal models of the disease. In
patients, this may contribute to serious long-term complications,
such as severe hepatomegaly, hepatic adenomas, and hepatocellular
carcinoma. Manifestations of the disease begin to appear
shortly after birth and continue through adolescence into
adulthood. There is currently no approved therapy for GSD Ia.
VK2809's potential to rapidly reduce hepatic triglyceride levels,
as demonstrated in this initial evaluation in a GSD Ia model,
provide support for the continued investigation of the compound in
this indication.
The proof-of-concept study was conducted under a sponsored
research agreement between Duke
University and Viking Therapeutics and designed to evaluate
the effects of VK2809 in Duke
University's G6PC knockout mouse model. The G6PC
knockout model is intended to replicate many of the same
biochemical and physiological characteristics present in GSD Ia
patients. In addition to the G6PC knockout mice, researchers
also included wild type mice in the study to provide additional
points of comparison. Study mice, both G6PC knockout and wild
type, received VK2809 or vehicle once-daily and subsequently
evaluated for changes in various measures of disease, including
liver size, weight, and triglyceride content.
VK2809 is a novel, orally available small molecule thyroid
receptor beta (TRβ) agonist that possesses selectivity for liver
tissue, as well as the beta receptor subtype, suggesting promising
therapeutic potential in a range of lipid disorders. Viking
is currently evaluating VK2809 in a randomized, double-blind,
placebo-controlled, parallel group Phase 2 study designed to assess
the drug candidate's efficacy, safety and tolerability in patients
with elevated LDL-C and non-alcoholic fatty liver disease.
Previously reported clinical data have demonstrated that treatment
with VK2809 leads to significant reductions in plasma
triglycerides, LDL cholesterol (LDL-C), and atherogenic protein
levels in subjects with mild hypercholesterolemia.
About GSD Ia
Glycogen storage disease Ia (GSD Ia) is a
rare, orphan genetic disease caused by a deficiency of
glucose-6-phosphatase (G6PC), an enzyme responsible for the liver's
production of free glucose from glycogen and gluconeogenesis.
The disease, for which there is no approved treatment, results in
an excess accumulation of glycogen and lipids in the liver,
potentially leading to hepatosteatosis, liver failure, development
of hepatic adenomas, and hepatocellular carcinoma. Increased
triglyceride production and elevated hepatic triglyceride levels
are characteristic of GSD Ia and associated with many
manifestations of the disease. GSD Ia is estimated to occur
in approximately 1 in every 50,000 – 100,000 births in the United
States. As manifestations of the disease begin to present
themselves at birth, a sizeable portion of GSD Ia patients are
children.
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 non-alcoholic 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 VK2809 and VK2809'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 VK2809; risks that prior clinical and
pre-clinical results 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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