CUPERTINO, Calif., Sept. 17, 2019 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today announced that it has
completed the Phase 2a clinical trial of its lead product
candidate, DUR-928, in patients with alcoholic hepatitis (AH). The
final enrollment for the trial consists of 12 severe patients (MELD
21-30) and 7 moderate patients (MELD 11-20) for a total of 19 AH
patients.
Clinical data from the trial show that the 19 patients treated
with DUR-928 had statistically significantly greater reductions
from baseline in bilirubin (day 7 and 28) and MELD (day 28), as
well as statistically significantly lower Lille scores, compared with a historical
control group (n=15) from a University of
Louisville (UL) AH
study.1
Lille scores are used in
clinical practice to help determine the prognosis for AH patients
after 7 days of treatment. The lower the Lille score, the better the prognosis is for
the AH patient. Patients with a Lille score below 0.45 have an 85% 6-month
survival rate vs. those with Lille
scores of above 0.45, who have only a 25% 6-month survival rate
(Louvet A et al. Hepatology 2007; 45: 1348-54). In our study, the
median Lille score for the 18 AH
patients treated with DUR-928 who returned for their Day 7
visit2 was 0.10. Eighty nine percent (16/18) had a
Lille score below 0.45. The median
Lille score among the UL cohort of
15 patients treated with either supportive care or supportive care
with corticosteroids was 0.41, with 53% (8/15) having a
Lille score below 0.45.
DUR-928 was well tolerated in all patients, with no drug-related
serious adverse events reported at any dose level. Drug exposures
were dose proportional and were uninfluenced by the severity of the
disease.
"We are excited that the first trial of DUR-928 in AH patients
demonstrated superior outcomes compared to historical control
data," said James E. Brown,
President and CEO of DURECT. "DUR-928 was well tolerated at all
dose levels tested and we have gained valuable information to help
support dose selection in the next study. We look forward to
completing our analysis and reporting additional data at the
upcoming AASLD Liver Meeting in Boston in November."
"AH is a devastating acute condition with high mortality rates
and limited therapeutic options," continued Dr. Brown. "We are
planning to meet with the FDA to discuss the design of the next
DUR-928 AH clinical trial as well as the regulatory path to
approval."
About the DUR-928 Alcoholic Hepatitis Phase 2a
Trial
Patients with moderate and severe AH were treated with
intravenously administered DUR-928 in this open label, dose
escalation multi-center U.S., Phase 2a clinical trial. Final
enrollment was 19 patients comprised of: 8 patients (4 moderate and
4 severe) dosed at 30 mg, 7 patients (3 moderate and 4 severe)
dosed at 90 mg and 4 patients (4 severe) dosed at 150 mg.
Throughout the study, prior to initiating a higher dose, safety and
PK results of the prior dose level were reviewed by a Dose
Escalation Committee (DEC). The DEC also reviewed safety and PK
data from the patients treated at the 150mg dose and reported that
there were no drug-related serious adverse events throughout the
study at any dose. The study objectives included assessment of
safety, PK and pharmacodynamic (PD) signals, including liver
chemistry and biomarkers.
About DURECT Corporation
DURECT is a biopharmaceutical company actively developing
therapeutics based on its Epigenetic Regulator Program and
proprietary drug delivery platforms. DUR‑928, a new chemical
entity in Phase 2 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 such as alcoholic Hepatitis (AH) and
acute kidney injury (AKI), chronic hepatic diseases such as
nonalcoholic steatohepatitis (NASH), and inflammatory skin
conditions such as psoriasis and atopic dermatitis. DURECT's
advanced oral and injectable delivery technologies are designed to
enable new indications and enhanced attributes for small-molecule
and biologic drugs. Key product candidates in this category
include POSIMIR® (bupivacaine extended-release
solution), an investigational locally-acting, non-opioid analgesic
intended to provide up to 3 days of continuous pain relief after
surgery, a long-acting injectable SABER-based HIV product being
developed with Gilead, and ORADUR™-Methylphenidate ER
Capsules, approved in Taiwan as
Methydur Sustained Release Capsules, where it is indicated for the
treatment of attention deficit hyperactivity disorder (ADHD).
In addition, for the assignment of certain patent rights, DURECT
receives single digit sales-based earn-out payments from U.S. net
sales of Indivior's PERSERIS™ (risperidone) drug for
schizophrenia, which was commercially launched in February
2019. For more information about DURECT, please visit
www.durect.com.
NOTE: POSIMIR®, SABER® and
ORADUR™ are trademarks of DURECT Corporation. Other
referenced trademarks belong to their respective owners. DUR-928
and POSIMIR 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 plans,
preliminary data and initial results from the Phase 2a trial of
DUR-928 in patients with AH are forward looking statements, which
are subject to risks and uncertainties. These risks and
uncertainties include, but are not limited to, the risk that
results from this clinical trial may not be replicated in future
clinical trials, including in trials with larger numbers of
patients. This press release also includes additional
forward-looking statements, including regarding clinical trial
plans for DUR-928, the potential use of DUR-928 to treat AH, AKI,
chronic hepatic diseases such as NASH, and inflammatory skin
disorders such as psoriasis and atopic dermatitis, as well as
statements regarding the use of POSIMIR to treat post-surgical
pain, the use of Methydur to treat ADHD, and potential earn-out
payments from U.S. sales of PERSERIS. These forward-looking
statements involve 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 risk of delays in the enrollment of the ongoing
clinical trials of DUR-928 in NASH and psoriasis, potential adverse
effects arising from the testing or use of DUR-928, the risk that
the FDA may not approve the POSIMIR NDA, the risk that PERSERIS and
Methydur will not be successfully commercialized, our ability to
avoid infringing patents held by other parties and secure and
defend patents of our own patents, and our ability to manage and
obtain capital to fund our operations and expenses. Further
information regarding these and other risks is included in DURECT's
Form 10-Q filed with the Securities and Exchange Commission on
August 2, 2019 under the heading
"Risk Factors."
1 Our advisor, Dr. Craig
McClain from the University of
Louisville (UL), shared anonymized data from his study, in
which 15 AH patients with initial MELD scores ranging from 15-30
received either supportive care alone (n=8) or supportive care with
corticosteroids (n=7).
2 One patient did not return for the day 7 visit,
so Lille scores could only be
calculated for 18 of 19 patients.
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SOURCE DURECT Corporation