CUPERTINO, Calif., April 24, 2017 /PRNewswire/ -- DURECT Corporation
(Nasdaq: DRRX), a biopharmaceutical company actively developing new
therapeutics based on its Epigenetic Regulator Program and
proprietary drug delivery platforms, announced that clinical data
on DUR-928 were presented at The International Liver
CongressTM 2017 (the 52nd annual meeting of
the European Association for the Study of the Liver (EASL)) on
April 22 in Amsterdam.
"DUR-928 was well tolerated in this study and plasma exposure of
the molecule was not significantly increased in NASH patients
compared to matched control subjects with normal liver function,"
stated James E. Brown, D.V.M.,
President and CEO of DURECT. "Importantly, treatment with a
single dose of DUR-928 was associated with a decrease in cell death
markers, an improvement of a biomarker of liver function, and
decreases in certain biomarkers associated with inflammation."
Phase 1b trial in patients with NASH
The study was a Phase 1b single dose ranging (50 mg and 200 mg),
safety and pharmacokinetic (PK) study of orally-administered
DUR-928 in two cohorts of biopsy-confirmed NASH patients and
matched control subjects (MCS) (matched by age, BMI, and gender)
with normal liver function. Both cohorts consisted of 10 NASH
patients and 6 MCS.
In both cohorts, DUR-928 was well tolerated overall. There was
approximately a 10-30% increase in DUR-928 exposure in NASH
patients compared to MCS. A single serious adverse event (shortness
of breath), designated as possibly related to study drug, was
reported in Cohort 2 in a NASH patient with a prior history of
arrhythmia and an ongoing viral infection; no unusual abnormal
biochemistry was observed and the symptom spontaneously
resolved.
Exploratory biomarker analysis indicated that a single oral dose
of DUR-928 resulted in reductions from baseline in the levels of
both full-length and cleaved cytokeratin-18 (CK-18), bilirubin,
hsCRP and IL-18 in NASH patients.
- The decrease of full-length CK-18 (a generalized cell death
marker) at 12 hours was approximately 33% in the NASH patients in the low dose
cohort and approximately 41% in the
high dose cohort. The decrease of cleaved CK-18 (a cell apoptosis
marker) at 12 hours was approximately 37% in the NASH patients in the low dose
cohort and approximately 47% in the
high dose cohort.
- The decrease in total bilirubin (a liver function marker for
which a decrease would be seen as positive) at 12 hours in the NASH
patients was approximately 27% in the low dose cohort and
approximately 31% in the high dose cohort.
- High sensitivity C-Reactive Protein (hsCRP), a marker of
inflammation, trended higher at 12 hours in the NASH patients by
approximately 3% in the low dose cohort but trended lower by
approximately 12% in the high dose cohort.
- IL-18, an inflammatory mediator implicated in both liver and
kidney diseases, trended lower at 12 hours by approximately 5% in
both the low dose cohort and in the high dose cohort.
Collectively, the reduction of these biomarkers, together with
results from DURECT's animal and cell culture studies, suggest
potential therapeutic activity of DUR-928 in patients with liver
disease. However, additional studies, including larger
controlled trials, will be required to confirm these findings and
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.
The poster that was presented at ILC 2017 will shortly be posted
to the "Science & Technologies" section of DURECT's website at
www.durect.com.
About DURECT
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, chronic metabolic diseases such as
nonalcoholic fatty liver disease (NAFLD), nonalcoholic
steatohepatitis (NASH) and other liver diseases with both broad and
orphan populations, and inflammatory skin conditions such as
psoriasis. 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 product candidate in this category is
POSIMIR® (SABER®-Bupivacaine), an
investigational locally-acting, non-opioid analgesic intended to
provide up to 3 days of continuous pain relief after surgery.
Another late stage product candidate is REMOXY® ER
(oxycodone), an investigational pain control 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 disorders of the liver,
acute organ injury, kidney diseases or psoriasis or other
inflammatory conditions, the potential use of POSIMIR and REMOXY ER
to treat pain, and potential markets for our product candidates 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 replicate results reported here or do not
demonstrate the safety or efficacy of DUR-928 in a statistically
significant manner, the risk of delays in the commencement,
enrollment or completion of clinical 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 our drug candidates, our
potential failure to maintain our collaborative agreements with
third parties or consummate new collaborations 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-K filed on March 29,
2017 under the heading "Risk Factors."
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SOURCE DURECT Corporation