SAN DIEGO, Oct. 24, 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 final results from an eight-week study of VK2809 in an
in vivo model of non-alcoholic steatohepatitis (NASH).
Data from this study demonstrated statistically significant
improvements in several key measures relevant to the development
and progression of NASH. Additionally, an evaluation of gene
expression changes demonstrated statistically significant changes
in the expression of multiple genes associated with the development
and progression of NASH following eight weeks of treatment with
VK2809, as compared to vehicle control. The results were
presented in a poster presentation at The Liver Meeting®
2017, the annual meeting of the American Association for the Study
of Liver Diseases (AASLD), held October
20-24, 2017, in Washington,
D.C.
Key results from the study included:
- Treatment with VK2809 resulted in statistically significant
reductions in liver triglycerides, liver cholesterol, total lipids
and non-alcoholic fatty liver disease activity score (NAS) in
treated animals relative to vehicle controls. As summarized
below, VK2809-treated animals demonstrated:
-
- An 80% reduction in total lipid content vs. vehicle controls (p
< 0.0001)
- A 70% reduction in liver triglyceride content vs. vehicle
controls (p < 0.0001)
- A 65% reduction in liver cholesterol content vs. vehicle
controls (p < 0.0001)
- A 40% reduction in NAS, a composite of disease activity
comprised of steatosis, ballooning and inflammation, vs. vehicle
controls (p < 0.0001)
- Treatment with VK2809 resulted in statistically significant
reductions in several key measures of fibrotic activity, including
total liver fibrosis, type I collagen and hydroxyproline, relative
to vehicle controls. As summarized below, VK2809-treated
animals demonstrated:
-
- A 50% reduction in total liver fibrosis vs. vehicle controls (p
< 0.01)
- A 60% reduction in type I collagen vs. vehicle controls (p <
0.005)
- A 46% reduction in liver hydroxyproline content vs. vehicle
controls (p < 0.01)
- Treatment with VK2809 resulted in statistically significant
changes in the expression of key genes associated with NASH
development and progression, relative to vehicle controls. As
summarized below, VK2809-treated animals demonstrated:
-
- Reductions of 44% and 37% in SREBF1 and SCD1 expression,
respectively, and a 74% increase in CYP7a expression (p < 0.01
for each), suggesting improved lipid and cholesterol
metabolism
- Increases of 337% and 64% in FGF21 and PPARδ expression,
respectively (p < 0.01 for each), suggesting improved lipid
metabolism and insulin sensitivity
- Reductions of 40%, 42%, and 18% in ANXA2, CK-18, and ASK1
expression (p < 0.01 for each), suggesting reduced inflammation,
apoptosis and oxidative stress
- Reductions of 36%, 37%, and 65% in pro-fibrogenic genes Col1a1,
αSMA, and Galectin 1, respectively (p < 0.01, p < 0.05, p
< 0.001, respectively), suggesting reduced fibrotic
activity
"These results demonstrate the promise of VK2809 in a
biopsy-confirmed model of diet-induced NASH, showing impressive
lipid-lowering effects, as well as anti-fibrotic benefits," said
Brian Lian, Ph.D., chief executive
officer of Viking. "The observed changes in gene expression
are exciting, as they corroborate the histologic improvements and
suggest potential benefits on insulin sensitivity and metabolic
control. VK2809's therapeutic and safety profile continue to
suggest a promising potential role in settings such as NASH and
hyperlipidemia."
Presented study results also highlighted that treatment with
VK2809 was safe and well-tolerated, with no significant changes to
liver function tests observed relative to controls.
Additionally, data showed that VK2809 compared favorably to the
study's active control treatment, a PPAR-targeting agent that is
currently in late-stage clinical development.
The study was designed to evaluate VK2809 dosed orally (10
mg/kg/day) for eight weeks in a mouse model of diet-induced
NASH.1 Control cohorts received either vehicle or
active control. Animals were biopsied prior to treatment to
ensure disease characteristics consistent with the human form of
disease, including the presence of fibrosis. Changes in gene
expression were evaluated by assessing changes in RNA expression at
the conclusion of the experiment, compared with vehicle-treated
controls.
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 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 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.
References:
1. N.M. Kristiansen, S.S. Veidal,
et al., Obese diet-induced mouse models of non-alcoholic
steatohepatitis-tracking disease by liver biopsy, World J.
Hepatology, 2016; 8(16):673-684. M. Reigh, K.S. Tobol, et al., Comparative effects of
liraglutide, elafibranor, and obeticholic acid on NAFLD activity
score and fibrosis stage in a diet-induced obese mouse model of
biopsy-confirmed NASH; Hepatology 66(1): S599, 2017.
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SOURCE Viking Therapeutics, Inc.