Presentation Highlights Previously Reported
Weight Loss of up to 7.8% From Baseline as well as Significant
Liver Fat, Plasma Lipid Reductions following 28 Days of Treatment
with VK2735
SAN
DIEGO, Oct. 17, 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
that new results from the company's Phase 1 single ascending dose
(SAD) and multiple ascending dose (MAD) clinical trial of VK2735
were featured in an oral presentation at ObesityWeek 2023, the
annual meeting of The Obesity Society. VK2735 is a novel dual
agonist of the glucagon-like peptide 1 (GLP-1) and
glucose-dependent insulinotropic polypeptide (GIP) receptors in
development for the potential treatment of various metabolic
disorders such as obesity.
Highlights from the oral presentation include newly reported
data demonstrating that 28 days of once-weekly treatment with
VK2735 resulted in reductions in subjects' liver fat content and
plasma lipid levels, both from baseline and as compared to
placebo.
Data presented at ObestityWeek 2023 include:
Reduction in Liver Fat Content
Following 28 days of once-weekly treatment with VK2735, study
results demonstrated reductions in liver fat content, both as
compared to baseline and as compared to placebo. Subjects
receiving VK2735 experienced reductions in liver fat ranging up to
47.2% from baseline.
In the subgroup of study subjects with non-alcoholic fatty liver
disease (NAFLD), defined as those with greater than 5% liver fat at
baseline, the reductions in liver fat levels were more
pronounced. For these subjects, reductions from baseline
after four weekly doses ranged up to 49.7%, and placebo-adjusted
reductions of up to 58.5% were reported. These results suggest that
treatment with VK2735 may provide benefit among patients with NAFLD
or non-alcoholic steatohepatitis (NASH).
Change in Liver Fat Content Following 28 Days of Dosing with
VK2735
Multiple Ascending Dose
Level
|
Placebo
(n=8)
|
VK2735 0.5
mg
(n=6)
|
VK2735 1.5
mg
(n=6)
|
VK2735 1.5/3/5/5
mg2
(n=6)
|
VK2735 3/5/5/7.5
mg
(n=6)
|
VK2735 5/5/7.5/10
mg
(n=4)
|
Mean baseline liver fat
content (%)1
|
6.59
|
2.58
|
7.84
|
8.14
|
11.1
|
3.96
|
Mean percent change
from baseline 3
|
-0.7
|
3.9
|
-24.2
|
-24.0
|
-47.2
|
-8.4
|
p-value vs.
placebo4
|
-
|
0.74
|
0.09
|
0.10
|
0.002
|
0.62
|
|
|
|
|
|
|
|
NAFLD subset
|
n=3
|
n=0
|
n=4
|
n=4
|
n=4
|
n=1
|
Mean baseline liver fat
content (%)1
|
12.7
|
-
|
10.6
|
10.6
|
15.2
|
7.7
|
Mean percent change
from baseline 3
|
8.8
|
-
|
-33.8
|
-32.5
|
-49.7
|
-10.7
|
p-value vs.
placebo4
|
-
|
-
|
0.03
|
0.03
|
0.006
|
-
|
Notes: 1) MRI-PDFF; all subjects enrolled in MAD portion of
study were required to have baseline BMI ≥30 kg/m2. 2)
Subjects received escalating weekly doses of 1.5 mg, 3.0 mg, 5.0
mg, 5.0 mg. 3) Least squares mean. 4) Two-sided t test using
ANCOVA.
Reduction in Plasma Lipid Levels
Study investigators also evaluated the change in subjects'
levels of plasma lipids, including apolipoprotein B (ApoB),
low-density lipoprotein cholesterol (LDL-C), and total cholesterol,
following 28 days of once-weekly treatment with VK2735. Dose
dependent reductions from baseline in these plasma lipid levels
were observed across VK2735 treatment cohorts after four weekly
doses. No meaningful changes in levels of high-density
lipoprotein cholesterol (HDL-C) were observed following treatment
with VK2735.
Change in Plasma Lipids Following 28 Days of Dosing with
VK2735
Multiple Ascending Dose
Level
|
Placebo
(n=9)
|
VK2735 0.5
mg
(n=6)
|
VK2735 1.5
mg
(n=6)
|
VK2735 1.5/3/5/5
mg2
(n=6)
|
VK2735 3/5/5/7.5
mg
(n=6)
|
VK2735 5/5/7.5/10
mg
(n=4)
|
Mean change in Apo(B)
from baseline (%)1
|
1.8
|
3.3
|
-1.8
|
-12.9
|
-12.5*
|
-20.5
|
Mean change in LDL-C
from baseline (%)
|
-9.5
|
1.4
|
-10.6
|
-13.7
|
-20.3*
|
-23.0
|
Mean change in total
cholesterol from baseline (%)
|
-5.1
|
-1.7
|
-10.8
|
-14.9*
|
-17.4*
|
-21.0
|
Notes: *p<0.05 vs. baseline. 1) All subjects enrolled in MAD
portion of study were required to have baseline BMI ≥30
kg/m2. 2) Subjects received escalating weekly doses of
1.5 mg, 3.0 mg, 5.0 mg, 5.0 mg.
"These new data demonstrate VK2735's rapid and promising impact
on liver fat and plasma lipids on top of the previously reported
reductions in body weight," said Brian
Lian, Ph.D., chief executive officer of Viking
Therapeutics. "We believe these results suggest broader
potential benefits on a patient's overall metabolic health, in
tandem with weight loss, and may indicate utility in patients with
obesity, NAFLD, and NASH. We look forward to building upon
the Phase 1 data with results from our ongoing Phase 2 VENTURE
study, which is evaluating VK2735's safety and efficacy in patients
with obesity over a 13-week treatment period."
The ObesityWeek presentation also highlighted previously
reported safety, tolerability and weight loss results from the
Phase 1 SAD/MAD trial. In the 28-day MAD portion of the
study, VK2735 was well-tolerated and showed positive signs of
clinical activity. All MAD cohorts receiving VK2735
experienced reductions in mean body weight from baseline, ranging
up to 7.8%. Cohorts receiving VK2735 also demonstrated
reductions in mean body weight relative to placebo, ranging up to
6.0%. Statistically significant differences compared to
placebo were maintained or improved at the Day 43 follow-up time
point, 21 days after the last dose of VK2735 was administered. The
majority of observed adverse events (98%) in the Phase 1 trial were
reported as mild or moderate. The majority of GI-specific
adverse events (99%) were also reported as mild or moderate.
Notably, despite robust activation of the incretin receptor
pathways, no hypoglycemia was reported. The company believes
that the tolerability data from the Phase 1 study indicate that
higher doses may be achieved with longer titration
windows.
The Phase 1 trial was a randomized, double-blind,
placebo-controlled SAD and MAD study in healthy adults. The SAD
portion of the study evaluated VK2735 in healthy adults, while the
MAD portion of the study enrolled healthy adults with a minimum
body mass index of 30 kilograms per meter squared. The primary
objectives of the study were to evaluate the safety and
tolerability of single and multiple doses of VK2735 administered
subcutaneously and identify suitable doses for further clinical
development. The secondary objective was to evaluate the
pharmacokinetics of VK2735 in healthy subjects. The SAD portion of
the study evaluated escalating single doses of VK2735. In the MAD
portion of the study subjects received VK2735 once weekly for 28
days.
Viking is currently conducting the Phase 2 VENTURE trial, a
randomized, double-blind, placebo-controlled study to evaluate the
safety, tolerability, pharmacokinetics, and weight loss efficacy of
VK2735, administered subcutaneously, once weekly, for 13
weeks. The VENTURE trial is evaluating the treatment in
adults who are obese (BMI ≥30 kg/m2), or adults who are
overweight (BMI ≥27 kg/m2) with at least one
weight-related co-morbid condition. The primary endpoint of
the study is the percent change in body weight from baseline to
Week 13, with secondary and exploratory endpoints evaluating a
range of additional safety and efficacy measures.
About GLP-1 and Dual GLP-1/GIP Agonists
Activation of the glucagon-like peptide 1 (GLP-1) receptor has
been shown to decrease glucose, reduce appetite, lower body weight,
and improve insulin sensitivity in patients with type 2 diabetes,
obesity, or both. Semaglutide is a GLP-1 receptor agonist that has
been approved by the U.S. Food and Drug Administration and is
currently marketed in various dosage strengths and forms as
Ozempic®, Rybelsus®, and Wegovy®.
More recently, research efforts have explored the potential
co-activation of the glucose-dependent insulinotropic peptide (GIP)
receptor as a means of enhancing the therapeutic benefits of GLP-1
receptor activation. Tirzepatide is a dual GLP-1/GIP receptor
agonist that is currently in clinical development for obesity.
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.
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 and cash
resources. 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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