CUPERTINO, Calif., Nov. 13, 2020 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today presented additional safety
data and efficacy signals from its Phase 1b clinical trial of DUR-928 in nonalcoholic
steatohepatitis (NASH) patients in a poster presentation at The
AASLD Liver Meeting Digital Experience ™ (TLMdX) 2020.
"The additional safety and efficacy data presented, including
improvements in multiple biomarkers of liver health such as a
significant reduction in cytokeratin-18 among the patients who also
experienced at least a 10% reduction in liver fat, continue to
strengthen the promising profile of DUR-928 for NASH," stated
Eric Lawitz, M.D., Texas Liver
Institute, University of Texas Health
San Antonio and principal investigator of the study. "Together with
previously reported overall global reduction from baseline of liver
enzymes, liver fat, stiffness as measured by imaging and serum
lipids, this additional biomarker data suggests that epigenetic
modulation by DUR-928 is worthy of further study in NASH
patients."
James E. Brown, D.V.M., President
and CEO of DURECT, added, "The safety and efficacy profiles
demonstrated with DUR-928 not only in this NASH trial but in our
Phase 2a trial in alcoholic hepatitis, demonstrate potential of
this epigenetic regulator to treat multiple acute organ injury and
chronic liver diseases. We look forward to continuing the
evaluation of DUR-928 in our clinical studies and potentially
bringing a life-saving treatment option to patients in need."
Data presented at The Liver Meeting further demonstrated that
DUR-928 was well tolerated at all three doses (50mg, 150mg, and
600mg) with no serious adverse events reported.
Improvements in Biomarkers Data Summary (Day 28 vs
Baseline)
% change from baseline at the end of dosing (median at day
28)
Biomarker
|
Daily Dose
(mg)
|
|
50
|
150
|
600
|
Cytokeratin 18
M30
|
-14.6
|
-8.6
|
-16.1
|
Cytokeratin 18
M65
|
-18.1
|
-9.9
|
-35.0
|
C Reactive
Protein
|
-13.9
|
-11.8
|
1.7
|
Plasminogen
Activator
Inhibitor-1
|
-13.5
|
-13.7
|
-8.2
|
Interleukin 1
Beta
|
-0.1
|
-0.6
|
-0.2
|
Interleukin
6
|
-6.0
|
1.7
|
5.4
|
Interleukin
12
|
0.0
|
0.0
|
0.0
|
Interleukin
17
|
-1.3
|
-16.4
|
-0.8
|
Interleukin
18
|
-8.9
|
-5.0
|
-2.1
|
Tumor Necrosis
Factor
|
-3.2
|
-2.9
|
-7.9
|
Bile
Acid
|
0.0
|
0.0
|
1.6
|
Adiponectin
|
-1.6
|
-3.8
|
3.9
|
Adiponectin,
HMW
|
0.0
|
1.0
|
1.0
|
Biomarker Data Along With Previously Reported Improvements in
Liver Enzymes, Imaging and Serum Levels (Day 28 vs
Baseline)
* Indicates p-value <0.05; ** indicates p < 0.01; ***
indicates p <0.001
Median
at Day
28
|
All
Subjects
|
Patients with ≥
10% Reduction in
MRI-PDFF
|
50 mg
QD
(n=21-23)
|
150 mg
QD
(n=20-21)
|
300 mg
BID
(n=20-21)
|
50 mg
QD
(n=9)
|
150 mg
QD
(n=8)
|
300 mg
BID
(n=9)
|
Liver
Enzymes
|
ALT
|
-16%*
|
-10%
|
-17%***
|
-21%**
|
-19%*
|
-32%***
|
AST
|
-14%
|
-9%
|
-18%**
|
-24%**
|
-21%
|
-39%***
|
GGT
|
-6%
|
-1%
|
-8%*
|
-13%***
|
-16%*
|
-14%
|
Imaging
|
MRI-PDFF
|
-7%
|
-7%
|
-4%
|
-18%***
|
-19%***
|
-23%***
|
FibroScan
|
-10%**
|
-9%
|
-1%
|
-7%
|
-9%**
|
-9%
|
Serum
Lipids
|
LDL-C
|
-6%
|
-11%*
|
-7%
|
-7%
|
-11%
|
-8%*
|
Non-HDL-C
|
-8%
|
-5%
|
-1%
|
-10%
|
-8%*
|
-12%*
|
Triglycerides
|
-13%*
|
-3%
|
-2%
|
-9%
|
0%
|
-8%
|
Biomarkers
|
CK-18,
M30
|
-14.6%
|
-8.6%
|
-16.1%
|
-22.8%***
|
-3.8%
|
-42.1%*
|
CK-18,
M65
|
-18.1%
|
-9.9%
|
-35.0%
|
-28.1%***
|
-8.7%
|
-55.8%*
|
ALT (alanine aminotransferase);
AST (aspartate aminotransferase); GGT (gamma-glutamyl
transferase); MRI-PDFF (Magnetic
Resonance Imaging - Proton Density Fat Fraction) is a
non-invasive measure of the proportion of liver tissue which is
composed of fat; FibroScan is a specialized
ultrasound machine that measures the stiffness of liver tissue.
LDL-C ( Low-Density Lipoprotein – Cholesterol);
Non-HDL-C (Total cholesterol excluding High-Density
Lipoprotein-Cholesterol); QD (once a day); BID (twice
a day); CK-18 (cytokeritin 18)
Additionally, in subjects with baseline triglyceride (TG) levels
≥200mg/dL (n=16), there was a 24% reduction at the end of the
4-week dosing period (p<0.01).
About DUR-928 Phase 1b
Trial
The study was a randomized, open label, multi center US study to
evaluate safety, pharmacokinetics and signals of biological
activity of DUR-928 in NASH patients with stage 1-3 fibrosis. A
total of 65 patients completed the study. DUR-928 was orally
administered daily at 50 mg (n=23), 150 mg (n=21), or 600 mg (300
mg BID (n=21)). Patients in this trial were dosed daily for 4 weeks
and followed up for an additional 4 weeks.
About DUR-928
DURECT's lead drug candidate, DUR-928, is an endogenous sulfated
oxysterol and an epigenetic regulator. It represents a new class of
therapeutics with a unique mechanism of action. DUR-928
epigenetically modulates the expression of multiple clusters of
master genes that are involved in many important cell signaling
pathways, through which it stabilizes mitochondria, reduces
lipotoxicity, regulates inflammatory or stress responses, and
promotes cell survival.
About NASH
Nonalcoholic steatohepatitis (NASH) is the most severe and
progressive form of nonalcoholic fatty liver disease (NAFLD) and
the most common chronic liver disease worldwide, with an estimated
prevalence of more than 10% of adults in the United States, Europe, Japan, and other developed countries, expected
to double by 2030. No drug is currently approved for treatment of
NAFLD or NASH.
About DURECT Corporation
DURECT is a biopharmaceutical company committed to transforming
the treatment of acute organ injury and chronic liver diseases by
advancing novel and potentially lifesaving therapies based on its
endogenous epigenetic regulator program. DUR-928, the company's
lead drug candidate is in clinical development for the potential
treatment of alcoholic hepatitis (AH), COVID-19 patients with acute
liver or kidney injury, and nonalcoholic steatohepatitis (NASH).
DURECT's proprietary drug delivery technologies are designed to
enable new indications and enhanced attributes for small-molecule
and biologic drugs. One late-stage product candidate in this
category is POSIMIR® (bupivacaine sustained-release solution), an
investigational locally-acting, non-opioid analgesic intended to
provide up to three days of continuous pain relief after surgery.
For more information about DURECT, please visit www.durect.com and
follow us on Twitter https://twitter.com/DURECTCorp.
DURECT Forward-Looking Statement
The statements in this press release regarding clinical
development plans for DUR-928, including the potential use of
DUR-928 to treat COVID-19 patients with liver or kidney injury, the
potential use of DUR-928 to treat acute organ injuries, such as AH,
and chronic liver diseases, such as NASH, the life saving potential
of DUR-928, and the potential use of POSIMIR to provide pain relief
after surgery are forward-looking statements involving risks and
uncertainties that can cause actual results to differ materially
from those in such forward-looking statements. Potential risks and
uncertainties include, but are not limited to, the risks that the
clinical trial of DUR-928 in COVID-19 patients is delayed or
stopped because of changes to the standard of care, the
availability of alternative therapies, protocol changes or lack of
available patients, the risk that future clinical trials of DUR-928
are not started when anticipated, take longer to conduct than
anticipated, do not confirm the results from earlier clinical or
pre-clinical trials, or do not demonstrate the safety or efficacy
or the life saving potential of DUR-928 in a statistically
significant manner, the risk that the FDA will not approve POSIMIR
or approve POSIMIR with a limited label, the risk that additional
time and resources may be required for development, testing and
regulatory approval of DUR-928 or the Company's other product
candidates, potential adverse effects arising from the testing or
use of our drug candidates, our potential failure to maintain our
collaborative agreements with third parties and risks related to
our ability to obtain capital to fund operations and expenses.
Further information regarding these and other risks is included in
DURECT's Form 10-Q filed on November 3,
2020 under the heading "Risk Factors."
NOTE: POSIMIR® and SABER® are trademarks
of DURECT Corporation. Other referenced trademarks belong to
their respective owners. DUR-928 and POSIMIR are
investigational drug candidates under development and have not been
approved for commercialization by the U.S. Food and Drug
Administration or other health authorities for any indication.
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