Late Breaking Poster Presentation Reports New
Results Demonstrating Robust Liver Fat Reductions Across Key
Subgroups, Including Patients with Type 2 Diabetes and Among Those
with F2 or F3 Fibrosis
Presentation also Highlights Previously
Reported Results Showing Successful Achievement of Study's Primary
Endpoint, Statistically Significant Liver Fat Reductions from
Baseline to Week 12 Among Patients Receiving VK2809
52-Week Biopsy Results Expected 1H
2024
SAN
DIEGO, Nov. 13, 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
the presentation of new results from the ongoing 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
latest findings from the VOYAGE study were featured in a late
breaking poster presentation at the Liver Meeting® 2023,
the annual meeting of the American Association for the Study of
Liver Diseases (AASLD), which is being held November 10-14, 2023, in Boston.
As previously reported, the VOYAGE 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. Newly reported
findings demonstrated robust and comparable liver fat reductions
among patients with or without type 2 diabetes, as well as patients
with either F2 or F3 fibrosis. These data demonstrate that VK2809's
potential therapeutic activity is not meaningfully impacted by the
presence of type 2 diabetes or by patients' stage of fibrosis. The
data are important as the presence of liver fat and
associated lipotoxicity are believed to play a contributing
role in the onset and progression of NASH.
Highlights from the AASLD presentation 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 magnetic resonance
imaging, proton density fat fraction (MRI-PDFF) relative to placebo
after 12 weeks of treatment. The median relative reduction
from baseline in liver fat ranged from 38% to 55% for patients
receiving VK2809. 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 a
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.
Among patients with type 2 diabetes, reductions from baseline in
liver fat were reported for all VK2809 cohorts, ranging from 36% to
54% at Week 12. The effect size among patients with type 2 diabetes
was comparable to that reported for patients without type 2
diabetes. Among non-diabetics, reductions in liver fat from
baseline ranged from 19% to 51%. These data suggest that activation
of the thyroid hormone beta receptor remains effective at reducing
liver fat in the presence of an important
metabolic comorbidity commonly observed in patients with
NASH.
Mean Reduction in Liver Fat Content at 12 Weeks in Patients
With and Without Type 2 Diabetes
|
Placebo
|
VK2809
1 mg
QD
|
VK2809
2.5 mg
QD
|
VK2809
5 mg
QOD
|
VK2809
10 mg
QOD
|
Patients with
Type 2 Diabetes
|
2.1 %
|
-35.8%*
|
-43.1%***
|
-39.5%***
|
-53.9%***
|
Patients without
Type 2 Diabetes
|
-6.2 %
|
-19.4 %
|
-47.0%***
|
-33.9%***
|
-51.2%***
|
Mean relative % change in liver fat at 12 weeks among patients
with and without type 2 diabetes. *p<0.05, ***p<0.001 vs.
placebo.
Treatment with VK2809 also demonstrated potent reductions in
liver fat content among patients with either F2 or F3 fibrosis.
Consistent with the efficacy observed among diabetics and
non-diabetics, these data suggest that VK2809 maintains potency
across a range of fibrosis stages.
Mean Reduction in Liver Fat Content at 12 Weeks in Patients
With F2 or F3 Fibrosis
|
Placebo
|
VK2809
1 mg
QD
|
VK2809
2.5 mg
QD
|
VK2809
5 mg
QOD
|
VK2809
10 mg
QOD
|
Patients with F2
Fibrosis
|
-7.8 %
|
-11.0 %
|
-44.9%***
|
-38.0%**
|
-49.2%***
|
Patients with F3
Fibrosis
|
-1.6 %
|
-21.1 %
|
-40.1%***
|
-39.0%***
|
-57.5%***
|
Mean relative % change in liver fat at 12 weeks among patients
with F2 and F3 fibrosis. **p<0.01 vs. placebo, ***p<0.001 vs.
placebo.
"We are pleased to see that the impressive efficacy demonstrated
by VK2809 for the VOYAGE study's primary endpoint remains
consistent across the study's key patient subpopulations.
Neither the presence of type 2 diabetes nor the presence of F2 or
F3 fibrosis meaningfully impacted VK2809's efficacy at reducing
liver fat. As steatosis and lipotoxicity are believed to be
underlying drivers in NASH, these data suggest benefits across
important disease subgroups," stated Brian
Lian, Ph.D., chief executive officer of Viking. "We look
forward to reporting 52-week biopsy data from VOYAGE in the first
half of 2024."
Safety and Tolerability
As previously reported, data from the VOYAGE study also
confirmed VK2809's encouraging safety and tolerability profile.
After 12 weeks, 94% of treatment related adverse events among
patients receiving VK2809 were reported as mild or moderate. As in
prior studies, VK2809 demonstrated excellent gastrointestinal
tolerability, with rates of nausea, diarrhea, stool frequency, and
vomiting similar among VK2809-treated patients compared to
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.
About VK2809
VK2809 is an orally available, tissue and receptor-subtype
selective agonist of the thyroid hormone 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 hormone 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.
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.
View original content to download
multimedia:https://www.prnewswire.com/news-releases/viking-therapeutics-presents-new-data-from-phase-2b-voyage-study-of-vk2809-in-patients-with-biopsy-confirmed-non-alcoholic-steatohepatitis-nash-at-the-liver-meeting-2023-301986439.html
SOURCE Viking Therapeutics, Inc