CUPERTINO, Calif., Aug. 27, 2020 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today announced the presentation of
pharmacokinetic (PK) data from a Phase 2a study of DUR-928 in
alcoholic hepatitis (AH) at the Digital International Liver
Congress™ 2020 (EASL), taking place on August 27-29. DUR-928 was well tolerated at
all doses tested in 19 AH patients, including 12 severe AH
patients. These PK data, together with other available information
for the drug, have been used to inform dose selection in the
Company's upcoming Phase 2b study of
DUR-298 in AH, planned to begin in the second half of
2020.
DURECT's Phase 2a AH study was an open-label, multi-center, dose
escalation safety, PK and pharmacodynamic (PD) trial which
evaluated doses of 30, 90, or 150 mg of DUR-928 administered by
intravenous infusion for 2 hours on Day 1 and Day 4 (if still
hospitalized), with patients followed for 28 days.
Key results presented include:
- Mean baseline laboratory characteristics and prognostic
scores:
-
- Bilirubin 14.2 mg/dL, (upper limit of normal is 1.2 mg/dL)
- MELD (Model for End-Stage Liver Disease) score 22.3, (≥21 is
severe)
- Maddrey's Discriminant Function 53.4 (≥32 is severe AH)
- Drug exposure for DUR-928 (as measured by both AUC and Cmax)
was dose proportional and comparable between moderate and severe AH
patients.
- Due to the severe liver injury in AH patients, the systemic
clearance of DUR-928 was reduced resulting in an approximately
2-fold higher Cmax in these AH patients compared to healthy
subjects.
As previously reported, DUR-928 was well tolerated at all doses
tested. All patients treated with DUR-928 survived through the
28-day follow-up period. Patients treated with DUR-928 had a
statistically significant reduction from baseline in bilirubin at
days 7 and 28, and in model of end-stage liver disease (MELD) score
at day 28. There was a 100% treatment response rate (as
defined by Lille score <0.45)
in patients receiving 30 or 90 mg doses; and an 89% response rate
in all patients. 74% of all DUR-928 treated patients and 67%
of those with severe AH were discharged from the hospital within
four days after receiving a single dose of DUR-928. There were no
drug-related serious adverse events, discontinuations or early
withdrawals, or termination of study drug or study participation
due to adverse events.
"We are encouraged by the PK results presented at EASL which
demonstrate that DUR-928 was well tolerated at all doses tested in
AH patients and contributed to the dose selection in our upcoming
Phase 2b AH trial, which we look
forward to initiating in the upcoming months," stated James E. Brown, D.V.M., President and CEO of
DURECT.
About the DUR-928 Alcoholic Hepatitis Phase 2a
Trial
This open-label, dose escalation, multi-center
study was designed to determine the safety, pharmacokinetics (PK)
and pharmacodynamics (PD) of DUR-928 in AH patients following
treatment. This included assessing liver biochemistry, biomarkers,
and prognostic scores such as the Lille score. Final
enrollment included 19 patients with moderate and severe AH, who
were administered DUR-928 intravenously at three different doses.
Eight patients (four moderate and four severe) were dosed at 30mg,
seven patients (three moderate and four severe) were dosed at 90mg
and four patients (all severe) were dosed at 150mg. For more
information, refer to ClinicalTrials.gov identifier:
NCT03432260.
DUR-928: next steps in alcoholic hepatitis
DURECT is
finalizing its preparations to initiate a multi-center,
international, randomized, double blind, placebo-controlled Phase
2b clinical trial of DUR-928 in
severe AH patients later this year. Based on these results and
other information generated during the program, the 30 and 90 mg
doses have been selected for this next study. The primary endpoint
will be survival rate for patients treated with DUR-928 compared to
those treated with placebo. Further details of the trial design,
including the size of the trial and other trial parameters will be
provided at a future date.
About Alcoholic Hepatitis (AH)
AH is an acute form of alcoholic liver disease (ALD), associated
with long-term heavy intake of alcohol, and often occurs after a
recent period of increased alcohol consumption. AH is typically
characterized by recent onset jaundice and hepatic failure. An
analysis of 77 studies published between 1971 and 2016, which
included data from a total of 8,184 patients, showed the overall
mortality from AH was 26% at 28 days. According to the most recent
data provided by the Agency for Healthcare Research and
Quality (AHRQ), a part of the US Department of Health and
Human Services (HHS), there were over 117,000 hospitalizations
for patients with alcoholic hepatitis in 2016. From a recent
publication analyzing the mortality and costs associated with
alcoholic hepatitis, the cost per patient is estimated at
over $50,000 in the first year. Liver transplantation
usually involves a long waiting period, a burdensome selection
process and a costly procedure over $800,000.
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. DURECT's lead 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. This drug candidate is currently in
Phase 2 development for the treatment of alcoholic hepatitis (AH)
and the treatment of COVID-19 patients with acute liver or kidney
injury as well as Phase 1 development for the treatment of
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 extended-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 and plans for
DUR-928, including initiating a Phase 2b trial of DUR-928 in AH in the second half of
2020, and the potential benefits and uses of our drug candidates,
including the potential use of DUR-928 to treat acute organ
injuries such as AH and COVID-19 patients with acute liver or
kidney injury as well as chronic liver diseases such as NASH, and
the use of POSIMIR to treat pain 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 future clinical trials of DUR-928 are
not started or finalized when anticipated, take longer to conduct
than anticipated, do not generate similar positive results as
generated in earlier clinical or pre-clinical trials, or do not
demonstrate the safety or efficacy of DUR-928 in a statistically
significant manner, the risk that the FDA will not approve POSIMIR,
the risk of disruptions to our business operations resulting from
the COVID-19 pandemic, the risk that additional time and resources
may be required for development, testing and regulatory approval of
DUR-928 or POSIMIR, 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-Q
filed on August 4, 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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SOURCE DURECT Corporation