SAN DIEGO, June 6, 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 study of VK2809 in an in
vivo model of non-alcoholic steatohepatitis (NASH). Data
from this study demonstrated improvements across several key
measures relevant to the development and progression of NASH.
Animals receiving VK2809 experienced statistically significant
improvements in non-alcoholic fatty liver disease activity score
(NAS), liver collagen content, and liver fibrosis relative to
vehicle-treated controls. NAS is a composite measure of
disease activity which is comprised of steatosis, ballooning and
inflammation. These results represent the first evidence of a
thyromimetic agent providing histologic benefits in a NASH model,
including an improvement in fibrosis.
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 (a metabolic-targeting agent currently in late-stage
clinical development for NASH). Animals were biopsied prior
to treatment to ensure disease characteristics consistent with the
human form of disease, including the presence of
fibrosis.
A summary of preliminary findings is highlighted below:
- Liver triglyceride content was reduced by 70% compared to
vehicle control (p<0.0001), and by 56% compared to active
control (p<0.0001)
- Liver cholesterol content was reduced by 65% compared to
vehicle control (p<0.0001) and by 58% compared to active control
(p<0.0001)
- Liver fibrosis was reduced by 50% compared to vehicle control
(p=0.01) and by 21% compared to active control (p=0.3)
- Liver collagen content was reduced by 60% compared to vehicle
control (p<0.005) and by 49% compared to active control
(p=0.07)
- Liver hydroxyproline content was reduced by 46% compared to
vehicle control (p=0.01) and by 36% compared to active control
(p=0.06)
Additional data showed that animals treated with VK2809
experienced a 40% mean improvement in NAS after eight weeks,
compared to vehicle-treated controls (p<0.0001; average baseline
NAS 5.7; n = 12/cohort); and 50% of VK2809-treated animals
demonstrated at least a two-point improvement in NAS, compared with
no vehicle-treated animals demonstrating at least a two-point
improvement (p=0.01). No animals treated with VK2809
demonstrated a worsening in NAS vs. approximately 60% of
vehicle-treated animals demonstrating a worsening
(p<0.0001). Improvements in all subcomponents of NAS
(inflammation, ballooning, and steatosis) were observed in
VK2809-treated animals relative to vehicle controls.
Consistent with previously-reported data, treatment with
VK2809 also produced significant reductions in plasma triglycerides
and cholesterol in this study. In addition, VK2809
demonstrated promising safety and tolerability. All animals
received all scheduled doses of drug and there were no unexpected
or abnormal laboratory findings.
"The preliminary data from VK2809 in this model of diet-induced
NASH demonstrate promising results in the quantitative resolution
of collagen, a major component of fibrosis, as well as significant
improvements in intracellular fat content," stated Joel Lavine, MD, PhD, Chief of Pediatric
Gastroenterology, Hepatology, and Nutrition at New
York-Presbyterian/Morgan Stanley Children's Hospital. "These
represent important elements of NASH and it will be interesting to
see additional studies conducted with VK2809 in this setting."
"We are excited about the initial results from this study, as
they demonstrate promising effects in a model of NASH that we
believe reflects many characteristics of the disease in humans,"
said Brian Lian, Ph.D., chief
executive officer of Viking. "The robust effect across
multiple disease metrics, including reductions in collagen and
lipotoxic lipids suggests potential benefits on endpoints important
in NASH. The observed reductions in hepatic collagen content
and fibrosis, by morphometric analysis, are particularly
noteworthy, as these data represent the first quantitative
histologic evidence that treatment with a thyromimetic agent can
potentially improve NASH-related fibrosis. These results
provide further support for the development of VK2809 in these
settings."
Scientific literature suggests that liver fibrosis is associated
with long-term outcomes in patients with non-alcoholic fatty liver
disease and that hepatic collagen content is correlated with
fibrosis staging and outcomes in these
patients.2,3,4 In addition, recently-published
data have indicated that a reduction of de novo lipogenesis can
produce improvements in markers of liver fibrosis in patients with
NASH.5 These data provide support for the
potential benefits of VK2809 in NASH, as prior data have shown that
VK2809 downregulates genes important for de novo lipogenesis, while
simultaneously stimulating the expression of genes important for
lipid metabolism. An analysis of genetic markers from the
current study is ongoing.
"The totality of published literature, combined with the effect
of VK2809 on hepatic lipids, collagen content, fibrosis and NAS
observed in the diet-induced disease model suggest an encouraging
potential benefit in NASH," stated Dr. Lian.
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
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.
2. P. Angulo, D.E. Kleiner, et
al., Liver Fibrosis, but no Other Histologic Features, Associates
with Long-term Outcomes of Patients With Nonalcoholic Fatty Liver
Disease; Gastroenterology 2015 August; 149(2): 389–397.e10.
3. Z.D. Goodman, L. Alaparthi, et
al., Correlations between hepatic morphometric collagen content,
histologic fibrosis staging, and serum markers in patients with
advanced fibrosis due to nonalcoholic steatohepatitis (NASH);
Hepatology 62(2):906A, October
2015.
4. E. Buzzetti, A. Hall, et al., Collagen proportion area is an
independent predictor of long-term outcome in patients with
non-alcoholic fatty liver disease; Hepatology 66(1): S52, 2017.
5. E.J. Lawitz, F. Poordad, A.
Coste et al., Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads
to significant improvements in MRI-PDFF, MRE, and other markers of
fibrosis after 12 weeks of therapy in patients with NASH;
Hepatology 66(1): S33, 2017.
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SOURCE Viking Therapeutics, Inc.