CUPERTINO, Calif., Jan. 30, 2017 /PRNewswire/ -- DURECT Corporation
(Nasdaq: DRRX) today provided an update on the DUR-928 development
program. DUR-928, our Epigenetic Regulator Program's lead
product candidate, is an endogenous, small molecule, new chemical
entity (NCE), which may have broad applicability in several
metabolic diseases such as nonalcoholic steatohepatitis (NASH) and
other liver conditions, and in acute organ injuries such as acute
kidney injury (AKI).
Phase 1b trial in patients with NASH
Our first patient trial utilizing DUR-928 was an open-label,
single-ascending-dose safety and pharmacokinetic (PK) Phase 1b
trial in liver function impaired (NASH) patients and matched
control subjects (matched by age, body mass index and gender with
normal liver function). This study was conducted in
Australia in successive cohorts
evaluating single-dose levels (first a low dose and then a high
dose) of orally administered DUR-928.
An abstract for this study has been accepted and data from
the study will be presented at the International Liver Congress™
2017 organized by the European Association for the Study of the
Liver (EASL) in Amsterdam,
April 19-23, 2017.
The low dose cohort consisted of 10 subjects with NASH (of which
4 were cirrhotic and 6 were not cirrhotic) and 6 matched control
subjects. After a PK/safety review of this cohort, the study
proceeded to the high dose cohort utilizing a dose four times
larger than the low dose cohort. The high dose cohort
consisted of 10 subjects with NASH (of which 2 were cirrhotic and 8
were not cirrhotic) and 6 matched control subjects. One
patient (with a prior history of arrhythmia and an ongoing viral
infection) in the high dose cohort experienced a serious adverse
event (shortness of breath) which occurred without unusual
biochemical changes and resolved without intervention but was
considered possibly treatment related by the physician due to its
temporal association with dosing. In both the low and high
dose cohorts, the PK parameters were comparable between the NASH
patients and the matched control subjects. In addition, the
systemic exposure following the low and high doses of DUR-928 was
dose dependent.
While this study was not designed to assess efficacy, we do
observe a dose dependent reduction of certain biomarkers after a
single oral dose of DUR-928. In both cohorts, IL-18, an
inflammatory mediator implicated in both liver and kidney diseases,
decreased in the NASH patients. In addition, both full length
CK-18 (a generalized cell death marker) and cleaved CK-18 (a cell
apoptosis marker) were reduced after DUR-928 treatment, with the
effect more pronounced in NASH patients.
Collectively, the reduction of these biomarkers plus results
from our animal and cell culture studies suggest potential
therapeutic activity of DUR-928 for patients with liver
disease. However, additional studies are required to evaluate
the safety and efficacy of DUR-928, and there is no assurance that
these biomarker effects will be observed in a statistically
significant manner, or that DUR-928 will demonstrate safety or
efficacy in treating NASH or other liver diseases, in larger
controlled trials.
Phase 1b trial in patients with impaired kidney
function
Our second Phase 1b study with DUR-928, also being conducted in
Australia, is an open-label,
single-ascending-dose safety and pharmacokinetic study in patients
with impaired kidney function (stage 3 and 4 chronic kidney
disease) and matched control subjects (matched by age, body mass
and gender with normal kidney function). This study is being
conducted in successive cohorts evaluating single-dose levels
(first a low dose and then a high dose) of DUR-928 administered by
intramuscular injection.
The low dose cohort consisted of 6 kidney function impaired
patients and 3 matched control subjects. After a PK/safety
review of this cohort, the study has proceeded to the high dose
cohort utilizing a dose four times larger than the low dose
cohort. Data from the low dose cohort showed the PK
parameters between the kidney function impaired patients and the
matched control subjects were comparable.
The high dose cohort of this study is currently enrolling
patients. In addition, we have held a pre-IND meeting
with the Cardiovascular and Renal Products Division of the FDA, and
we are utilizing feedback from that meeting as well as from our
clinical advisors to prepare an IND which is required to enable a
future kidney disease clinical trial in the United States.
Future Development Plans
We have been working with our clinical advisors to design
several Phase 2 studies and are planning to submit INDs which are
required to enable these studies to take place in the United States in 2017. We submitted
an initial IND in late December 2016
for a proposed Phase 2 liver study. The FDA has requested
additional non-clinical information (drug-drug interaction data)
and has made suggestions as to modifications to our proposed
protocol. We are working to address FDA's request and
consulting with our clinical advisors to finalize the study
protocol.
About DURECT Corporation
DURECT is a biopharmaceutical company actively developing new
therapeutics based on its Epigenetic Regulator Program and
proprietary drug delivery platforms. DUR‑928, a new chemical
entity in Phase 1 development, is the lead candidate in DURECT's
Epigenetic Regulator Program. An endogenous, orally
bioavailable small molecule, DUR-928 has been shown in preclinical
studies to play an important regulatory role in lipid homeostasis,
inflammation, and cell survival. Human applications may
include acute organ injury and chronic metabolic diseases such as
nonalcoholic fatty liver disease (NAFLD) and nonalcoholic
steatohepatitis (NASH). DURECT's advanced oral, injectable,
and transdermal delivery technologies are designed to enable new
indications and enhanced attributes for small-molecule and biologic
drugs. One late-stage development program in this category is
POSIMIR® (SABER®-Bupivacaine), an
investigational analgesic product intended to address key unmet
needs in postoperative pain management. Another is
REMOXY® ER (oxycodone), an investigational new drug
based on DURECT's ORADUR® technology. For more
information, please visit www.durect.com.
NOTE: POSIMIR®, SABER®, and
ORADUR® are trademarks of DURECT Corporation. Other
referenced trademarks belong to their respective owners.
POSIMIR, DUR-928, and REMOXY ER are drug candidates under
development and have not been approved for commercialization by the
U.S. Food and Drug Administration or other health authorities.
DURECT Forward-Looking Statement
The statements in this press release regarding the potential
benefits and uses of our drug candidates, including the potential
use of DUR-928 to treat NASH, other liver disease or kidney
disease, plans for an IND and Phase 2 and other clinical trials of
DUR-928, the potential use of POSIMIR to treat pain, and
potential markets for DUR-928 and POSIMIR, 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 future clinical trials of DUR-928 do not
demonstrate the safety or efficacy of DUR-928 in a statistically
significant manner, that the PERSIST clinical trial of POSIMIR will
take longer to conduct than anticipated or result in data that will
not support a successful NDA resubmission or product approval, the
risk of delays in the commencement, enrollment or completion of
other clinical trials, the risk that prior clinical trials will not
be confirmed in subsequent trials, the potential failure of
clinical trials to meet their intended endpoints, the risk of
adverse decisions by regulatory agencies or delays and additional
costs due to requirements imposed by regulatory agencies,
additional time and resources that may be required for development,
testing and regulatory approval of DUR-928, potential adverse
effects arising from the testing or use of DUR-928 or our other
drug candidates, 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 1, 2016 under the heading
"Risk Factors."
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SOURCE DURECT Corporation