Study Achieves Primary Endpoint, Demonstrating
Statistically Significant Reductions in Liver Fat from Baseline to
Week 12 in Patients Receiving VK2809 as Compared to Placebo
Up to 52% Mean Liver Fat Reduction Observed in
VK2809-Treated Patients
Up to 85% of Patients Experienced at Least a
30% Relative Reduction in Liver Fat
Statistically Significant Reductions in LDL-C,
Triglycerides, and Atherogenic Lipoproteins Observed
Adverse Events, Including GI-Related AEs,
Similar Among VK2809-Treated Patients vs. Placebo
Conference Call Scheduled for 8:00 a.m. ET Today
SAN DIEGO, May 16, 2023 /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 its Phase 2b clinical trial of
VK2809, the company's novel liver-selective thyroid hormone
receptor beta agonist, in patients with biopsy-confirmed
non-alcoholic steatohepatitis (NASH). The study successfully
achieved its primary endpoint, with patients receiving VK2809
experiencing statistically significant reductions in liver fat
content from baseline to Week 12 as compared with placebo.
The median relative change from baseline in liver fat as
assessed by magnetic resonance imaging, proton density fat fraction
(MRI-PDFF) ranged from 38% to 55% for patients receiving VK2809.
Additionally, VK2809-treated patients demonstrated
statistically significant reductions in low-density lipoprotein
cholesterol (LDL-C), triglycerides, and atherogenic lipoproteins
compared with placebo. The company expects to submit the
results for presentation at a future medical conference.
Top-line study results include:
Primary Endpoint: Reduction in Liver Fat Content at 12
Weeks
Patients receiving VK2809 experienced statistically significant
reductions in liver fat content, as assessed by MRI-PDFF, relative
to placebo after 12 weeks of treatment. Importantly, up to
85% of patients receiving VK2809 experienced at least a 30%
relative reduction in liver fat content, a level of reduction that
is associated with greater likelihood of histologic response in
NASH.
|
Placebo
(n =
62)
|
VK2809
1 mg
QD
(n =
17)3,4
|
VK2809
2.5 mg
QD
(n =
58)
|
VK2809
5 mg
QOD
(n =
36)4
|
VK2809
10 mg
QOD
(n =
56)
|
Mean baseline
liver
fat content
|
20.4 %
|
21.7 %
|
20.2 %
|
18.4 %
|
21.5 %
|
Mean
relative
change in
liver
fat by MRI-
PDFF1,2
|
-3.7 %
|
-16.6%
(p=0.082)
|
-45.3%
(p<0.0001)
|
-36.8%
(p<0.0001)
|
-51.7%
(p<0.0001)
|
Median
relative
change in
liver
fat
|
-5.4 %
|
-37.5 %
|
-48.1 %
|
-42.5 %
|
-55.1 %
|
Percentage
of
patients
experiencing ≥
30%
reduction
in liver
fat2
|
13.6 %
|
52.9%
(p=0.0015)
|
77.6%
(p<0.0001)
|
66.7%
(p<0.0001)
|
84.9%
(p<0.0001)
|
Notes: Data from Full Analysis Dataset, defined as all
randomized patients who received a baseline and post-baseline MRI.
1) Least squares mean change from baseline using an Analysis of
Covariance (ANCOVA) model. 2) p-value vs. placebo. 3) Reduced size
cohort intended to identify a minimally effective dose. 4)
Enrollment suspended at approximately 50% of target to accelerate
study completion.
"These results demonstrate VK2809's impressive potency at
reducing liver fat, which we believe represent the largest
reductions reported for an oral agent at this stage of
development," stated Brian Lian,
Ph.D., chief executive officer of Viking. "The high response rates
observed in this study suggest improved probabilities of histologic
benefit, as has been demonstrated in published clinical
studies. In addition, VK2809's consistent effect at reducing
plasma lipids provides further support for its role in improving
the metabolic profile of patients suffering from NASH. These
results align well with those reported from our prior 12-week NAFLD
study, but in a more severe population and at lower doses.
VK2809's excellent safety and tolerability further establish its
best-in-class profile, with rates of drug-related adverse events,
including GI-related events such as nausea and diarrhea, that are
similar to placebo. We believe these data suggest important
benefits for patients with NASH, and look forward to reporting the
52-week biopsy data from this study in the first half of next
year."
Reduction in Plasma Lipids
Consistent with prior studies, patients receiving VK2809
demonstrated statistically significant placebo-adjusted reductions
in LDL-C ranging from 11% to 20%, as well as statistically
significant reductions in triglycerides and atherogenic proteins
such as apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], and
apolipoprotein C-III (ApoC-III). Reductions in these plasma
lipids improve a patient's overall cardiometabolic profile and may
reduce the risk of cardiovascular-related events.
Safety and Tolerability
VK2809 demonstrated encouraging safety and tolerability in this
study. The majority (94%) of treatment related adverse events
among patients receiving VK2809 were reported as mild or moderate.
Discontinuations due to adverse events were low and balanced
among placebo and treatment arms. One treatment-related
serious adverse event (SAE) was reported in a patient receiving
VK2809. A patient with a history of psychiatric disorders
reported a worsening of their symptoms. As in prior studies,
VK2809 demonstrated excellent gastrointestinal (GI) tolerability in
this study. Rates of nausea, diarrhea, stool frequency, and
vomiting were similar among VK2809-treated patients compared to
placebo.
|
Placebo
(n =
65)
|
VK2809
1 mg
QD
(n =
17)
|
VK2809
2.5 mg
QD
(n =
66)
|
VK2809
5 mg
QOD
(n =
37)
|
VK2809
10 mg
QOD
(n =
61)
|
VK2809
combined
(n=181)
|
Treatment
emergent
adverse
events,
TEAEs
(number of
subjects,
(%))1
|
47
(72.3 %)
|
14
(82.4 %)
|
52
(78.8 %)
|
29
(78.4 %)
|
54
(88.5 %)
|
149
(82.3 %)
|
Drug-related
TEAEs2
|
22
(33.8 %)
|
7
(41.2 %)
|
13
(19.7 %)
|
9
(24.3 %)
|
23
(37.7 %)
|
52
(28.7 %)
|
TEAEs leading
to
study
discontinuation
|
5
(7.7 %)
|
2
(11.8 %)
|
1
(1.5 %)
|
1
(2.7 %)
|
5
(8.2 %)
|
9
(5.0 %)
|
Drug-related
GI adverse
events
|
12
(18.5 %)
|
4
(23.5 %)
|
3
(4.5 %)
|
1
(2.7 %)
|
7
(11.5 %)
|
15
(8.3 %)
|
Nausea
|
5
(7.7 %)
|
2
(11.8 %)
|
2
(3.0 %)
|
1
(2.7 %)
|
3
(4.9 %)
|
8
(4.4 %)
|
Diarrhea
|
2
(3.1 %)
|
3
(17.6 %)
|
2
(3.0 %)
|
1
(2.7 %)
|
3
(4.9 %)
|
9
(5.0 %)
|
Notes: Study safety population, defined as all patients who were
randomized and received at least one dose of study drug. 1) Data as
of March 13, 2023. 2) Deemed by
investigator as possibly, probably, or definitely related to study
drug.
At the 12-week timepoint, there were no numerically or
clinically meaningful differences observed in levels of alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) among
patients receiving VK2809 compared with patients receiving
placebo. Similarly, levels of thyroid hormones such as
thyroid stimulating hormone (TSH), free thyroxine (fT4), and free
triiodothyronine (fT3) were relatively unchanged among VK2809
treated patients compared to patients receiving placebo.
Changes in vital signs, including blood pressure, heart rate, and
body weight were similar among patients receiving VK2809 as
compared to patients receiving placebo.
Study Design
The VOYAGE study is a randomized, double-blind,
placebo-controlled, multicenter, international trial designed to
assess the efficacy, safety and tolerability of VK2809 in patients
with biopsy-confirmed NASH and fibrosis. Enrollment included
patients with at least 8% liver fat content as measured by
MRI-PDFF, as well as F2 and F3 fibrosis. The study allowed
for up to 25% of enrolled patients to have F1 fibrosis provided
that they also possess at least one additional risk factor, such as
diabetes, obesity or hypertension, among others. The primary
endpoint of the study evaluated the change in liver fat content
from baseline to Week 12 in patients treated with VK2809 as
compared to patients receiving placebo. Secondary objectives
include the evaluation of histologic changes assessed by hepatic
biopsy after 52 weeks of treatment.
Conference Call Today at 8:00 a.m.
ET
Viking will hold a conference call today at
8:00 a.m. ET to discuss the top-line
results from the Phase 2b VOYAGE
study of VK2809. To participate on the conference call,
please dial 844-850-0543 from the U.S. or 412-317-5199 from
outside the U.S. In addition, following the completion of the
call, a telephone replay will be accessible until May 23, 2023 by dialing 877-344-7529 from the
U.S. or 412-317-0088 from outside the U.S. and entering conference
ID 2702919. Those interested in listening to the
conference call live via the internet may do so by visiting the
Investor Relations section of Viking's website at
www.vikingtherapeutics.com. An archive of the webcast will be
available for 7 days on the company's website at
www.vikingtherapeutics.com.
About VK2809
VK2809 is an orally available, tissue and receptor-subtype
selective agonist of the thyroid beta receptor (TRβ) that possesses
selectivity for liver tissue, as well as the beta receptor subtype,
suggesting promising therapeutic potential in a range of lipid
disorders. The compound is currently being evaluated in a Phase
2b clinical trial in patients with
biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis.
VK2809 successfully achieved primary and secondary endpoints in a
Phase 2a study for the treatment of patients with elevated LDL-C
and non-alcoholic fatty liver disease (NAFLD). Selective activation
of the thyroid beta receptor in liver tissue is believed to
favorably affect cholesterol and lipoprotein levels via multiple
mechanisms, including increasing the expression of genes associated
with lipid metabolism and clearance.
About Viking Therapeutics, Inc.
Viking Therapeutics is a clinical-stage biopharmaceutical
company focused on the development of novel first-in-class or
best-in-class therapies for the treatment of metabolic and
endocrine disorders, with three compounds currently in clinical
trials. Viking's research and development activities leverage
its expertise in metabolism to develop innovative therapeutics
designed to improve patients' lives. The company's clinical
programs include VK2809, a novel, orally available, small molecule
selective thyroid hormone receptor beta agonist for the treatment
of lipid and metabolic disorders, which is currently being
evaluated in a Phase 2b study for the treatment of
biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis.
In a Phase 2a trial for the treatment of non-alcoholic fatty liver
disease (NAFLD) and elevated LDL-C, patients who received VK2809
demonstrated statistically significant reductions in LDL-C and
liver fat content compared with patients who received placebo. The
company is also developing VK2735, a novel dual agonist of the
glucagon-like peptide 1 (GLP-1) and glucose-dependent
insulinotropic polypeptide (GIP) receptors for the potential
treatment of various metabolic disorders. Data from a Phase 1 trial
evaluating VK2735 (dosed subcutaneously) for metabolic disorders
demonstrated an encouraging safety and tolerability profile as well
as positive signs of clinical benefit. The company also recently
initiated a Phase 1 study to evaluate an oral formulation of
VK2735. In the rare disease space, the company is developing
VK0214, a novel, orally available, small molecule selective thyroid
hormone receptor beta agonist for the potential treatment of
X-linked adrenoleukodystrophy (X-ALD). VK0214 is currently
being evaluated in a Phase 1b clinical trial in patients
with the adrenomyeloneuropathy (AMN) form of X-ALD. The company
holds exclusive worldwide rights to a portfolio of five therapeutic
programs, including VK2809 and VK0214, which are based on small
molecules licensed from Ligand Pharmaceuticals Incorporated.
For more information about Viking Therapeutics, please
visit www.vikingtherapeutics.com. Follow Viking on Twitter
@Viking_VKTX.
Forward-Looking Statements
This press release contains forward-looking statements
regarding Viking Therapeutics, Inc., under the safe harbor
provisions of the U.S. Private Securities Litigation Reform Act of
1995, including statements about Viking's expectations regarding
its clinical and preclinical development programs. Forward-looking
statements are subject to risks and uncertainties that could cause
actual results to differ materially and adversely 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 VK2735, VK0214, VK2809, and the
company's other incretin receptor agonists; risks that prior
clinical and preclinical results may not be replicated; risks
regarding regulatory requirements; and other risks that are
described in Viking's most recent periodic reports filed with the
Securities and Exchange Commission, including Viking's Annual
Report on Form 10-K for the year ended December 31, 2022, and subsequent Quarterly
Reports on Form 10-Q, including the risk factors set forth in those
filings. These forward-looking statements speak only as of the date
hereof. Viking disclaims any obligation to update these
forward-looking statements except as required by law.
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