CUPERTINO, Calif., May 7, 2019 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today announced preliminary data from
the ongoing DUR-928 alcoholic hepatitis (AH) Phase 2a clinical
trial. On Wednesday, May
8th at 8:30 a.m. Eastern
Time, DURECT will host a Key Opinion Leader (KOL) and
earnings conference call, during which the Company will discuss
financial results for the first quarter of 2019, provide a
corporate business update, and present preliminary AH clinical
trial data via webcast. Also participating in the call will be
three KOLs on alcoholic hepatitis: Drs. Steven Flamm, Tarek
Hassanein, and Paul
Kwo. Dr. Kwo will present an overview of AH including
details on the disease and its progression, current treatment
options and new treatments in development. Drs. Hassanein and Flamm
will discuss their experience treating patients in the ongoing
DUR-928 AH clinical trial.
Preliminary Results
Ten patients have completed dosing with DUR-928 to date in the
ongoing open label, dose-escalation, multi-center U.S. trial. Eight
patients (4 moderate and 4 severe) have been treated with DUR-98 at
the 30 mg dose, and two patients (1 moderate and 1 severe) at the
90 mg dose.
Lille scores are used in
clinical practice to help determine the prognosis for AH patients
after 7 days of treatment. Patients with a Lille score below 0.45 have an 85% 6-month
survival rate vs. those with Lille
scores of above 0.45, have only a 25% 6-month survival rate
(Louvet A et al. Hepatology 2007; 45: 1348-54). The lower
the Lille score, the better the
prognosis is for the AH patient. In our study, the median
Lille score for the 9 AH patients
treated with DUR-928 who returned for their Day 7 visit is 0.04,
with a range of 0.01 to 0.19. The median Lille score among a cohort of 15 patients
treated with either supportive care or supportive care with
corticosteroids at the University of
Louisville (UL) is 0.41 (shown as historical control).
1
The chart below shows individual patient Lille scores plotted as a function of their
initial MELD scores.
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)
|
Of the 10 AH
patients dosed to date with DUR-928, one patient did not return for
the day 7 visit, so Lille scores could only be calculated for 9 of
10 patients.
|
3)
|
Lille scores in
the DUR-928 patients were significantly lower than that of the UL
patients (p=0.002; Wilcoxon's Signed Rank Test).
|
Mathurin et al. proposed three prognostic classifications of AH
patients in response to treatment based on Lille scores and their correlation with 28-day
survival rates from a meta-analysis of four randomized controlled
trials evaluating the effectiveness of corticosteroids in an
aggregate of 324 patients with severe AH. (Methurin P. et al.
Gut 2011; 60:255-260) The following table shows the percentage
of patients from three AH data sets, including DUR-928, in each
Mathurin classification based on patients' Lille scores. Seventy-eight percent (7/9) of
the DUR-928 treated AH patients with Lille scores are classified as complete
responders, 22% (2/9) are partial responders and none (0/9) were
null responders.
|
Percent of AH
Patients in each Classification (data from separate studies)
|
Lille
Score
|
Classification
a
|
28-Day
Survival Rate a
|
Prednisolone
(n=51)b
|
UL
(n=15)c
|
DUR-928
(n=9)d
|
≤0.16
|
Complete
Responder
|
91.1% ±
2.7%
|
49%
|
33%
|
78%
|
0.16-0.56
|
Partial
Responder
|
79.4%±
3.8%
|
43%
|
20%
|
22%
|
≥0.56
|
Null
Responder
|
53.3%±5.1%
|
8%
|
47%
|
0%
|
|
|
P<0.0001 (a)
|
|
P=0.002
(e)
|
|
|
a)
|
Mathurin, et. al.,
Gut 2011;60:255-260
|
b)
|
Mathurin,
"Selonsertib in Combination with Prednisolone for the Treatment of
Severe Alcoholic Hepatitis: A Phase 2 Randomized Controlled
Trial" presented at AASLD San Francisco November 2018. The table
presents patients from the control group – all treated with
corticosteroids (prednisolone + placebo). Initial MELD scores
in this study ranged from 19 to 24.
|
c)
|
See footnote 1 on
page 1. d) See footnote 2 on page 1. e) See
footnote 3 on page 1.
|
Bilirubin is formed by the breakdown of red blood cells in the
body. The level of total bilirubin in the blood is an indication of
how the liver is functioning. Compared to baseline (n=10) ,
the median reduction in total bilirubin in the DUR-928 treated
patients was 16% at Day 7 (n=9) and 41% at Day 28 (n=8) compared to
3% at Day 7 and 35% at Day 28 in the UL patients. The chart
below shows the percent change in total bilirubin at Day 7 and 28
compared to baseline (Day 0) for both the separate UL (as
historical control) and DUR-928 studies.
Model of End-Stage Liver Disease (MELD) score is another common
scoring system used to assess the severity and prognosis of AH
patients. Patients with MELD scores of 11-19 are classified as
having moderate AH and patients with MELD scores of 20-30 are
classified as having severe AH. As with Lille scores, the lower the MELD score, the
better the prognosis for the AH patient. In our study (shown
in the chart below), the median reduction from baseline (Day 0,
prior to treatment) (n=10) in MELD in the DUR-928 treated patients
was 4% at Day 7 (n=9) and 21% at Day 28 (n=8) compared to a 4%
increase at Day 7 and 6% reduction at Day 28 in the UL patients (as
historical control).
To date there is no statistical difference in the
pharmacokinetic profiles between moderate and severe AH patients
treated with DUR-928. There have been no drug-related adverse
events in the DUR-928 treated patients to date.
The data presented in this press release are preliminary and
will be finalized upon completion of the trial. There can be no
assurance that additional patients treated with DUR-928 will have
similar results as those reported here.
About the Ongoing DUR-928 Alcoholic Hepatitis Phase 2a
Trial
DURECT is conducting a Phase 2a clinical trial with intravenously
administered DUR-928 in patients with AH. This is an open
label, dose escalation (30, 90 and 150 mg), multi-center U.S. study
that is enrolling patients with moderate and severe AH. Dose
escalation may occur following review of safety and pharmacokinetic
(PK) results of the prior dose level by a Dose Escalation Committee
(DEC). The target number of patients for the study is 4 moderate
and 4 severe patients per dose group. The objectives include
assessment of safety, PK and pharmacodynamic (PD) signals,
including liver chemistry and biomarkers.
Conference Call
and Webcast with Slides
|
Wednesday, May
8th at 8:30 a.m. Eastern Time/5:30 a.m. Pacific
Time
|
Toll
Free:
|
888-882-4478
|
International:
|
323-794-2590
|
Conference
ID:
|
7156796
|
Webcast:
|
http://public.viavid.com/index.php?id=134476
|
A live audio webcast and data slide presentation will be
available by accessing DURECT's homepage at www.durect.com and
clicking "Investors." If you are unable to participate during
the live webcast, the call and slide presentation will be archived
on DURECT's website under "Event Calendar – Past Events" in the
"Investors" section.
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 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. Late stage 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, 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, please visit www.durect.com.
DURECT Forward-Looking Statement
The statements in this press release regarding preliminary data
from the ongoing Phase 2a trial of DUR-928 in patients with AH,
including data regarding Lille
scores, response rates and bilirubin and MELD reductions are
forward looking statements to the extent that they suggest that
they are predictive of results for the full trial or for the
outcomes of the patients whose data is reported. 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, that the remainder of the Phase 2a
clinical trial of DUR-928 in AH patients does not replicate the
interim results reported here, the risk of delays in the enrollment
of the ongoing clinical trials of DUR-928 in AH, 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 have successful
launches, 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 May 7, 2019
under the heading "Risk Factors."
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