CUPERTINO, Calif., May 7, 2019 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today announced financial results for
the three months ended March 31, 2019
and provided a corporate update, including preliminary data from
the ongoing DUR-928 Phase 2a alcoholic hepatitis (AH) trial.
- Total revenues were $4.1million
and net loss was $7.1million for the
three months ended March 31, 2019 as
compared to total revenues of $3.5
million and net loss of $8.3
million for the three months ended March 31, 2018.
- At March 31, 2019, cash and
investments were $28.8 million,
compared to cash and investments of $34.5
million at December 31, 2018.
Debt at March 31, 2019, including
partial accrual for the final payment of our term loan, was
$20.7 million.
"Several important development milestones were achieved during
the first quarter, including achieving impressive preliminary data
in the ongoing AH trial and initiating dosing in the NASH and
psoriasis clinical trials. We also made progress toward filing a
response to the POSIMIR CRL and strengthened our board with the
addition of two new members who bring valuable experience and
perspective." stated James E. Brown,
D.V.M., President and CEO of DURECT. "Thanks to the progress made
during the quarter, we have four potential major catalysts ahead of
us this year: additional AH data, readouts from the NASH and
psoriasis DUR-928 clincal trials, and a potential approval for
POSIMIR if our filing strategy is successful."
Update on Selected Programs and Transactions:
Epigenetic Regulator Program. DUR-928, the lead product
candidate in the Company's Epigenetic Regulator Program, is an
endogenous, first-in-class small molecule, which may have broad
applicability in chronic liver diseases such as NASH, in acute
organ injuries such as AH and acute kidney injury (AKI), and in
inflammatory skin disorders such as psoriasis and atopic
dermatitis.
Clinical Trials
Alcoholic Hepatitis (AH)
- Preliminary Data
-
- Ten patients have completed dosing with DUR-928 to date in the
ongoing Phase 2a 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, who have a 25%
6-month survival rate (Louvet A et al. Hepatology
2007; 45: 1348-54). In another study looking at 28-day
survival rates in severe AH patients, a Lille score of ≤0.16 is associated with a 91%
28-day survival rate; a Lille score of 0.16-0.56, 79% 28-day
survival rate and a Lille score of
≥0.56 is associated with a 53% 28-day survival rate.
(Mathurin, et. al., Gut 2011;60:255-260). The lower the
Lille score, the better the
prognosis is for the AH patient. 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. In the 9 patients with
Lille scores treated with DUR-928,
the median Lille score is 0.04,
with a range of 0.01 to 0.19.
- 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 initial MELD scores of 11-19 are classified
as having moderate AH and patients with initial 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. Compared to baseline
(prior to treatment) (n=10), the median reduction in MELD was 4% at
Day 7 (n=9) and 21% at Day 28 (n=8).
- 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 well the liver is functioning. Compared to baseline (n=10), the
median reduction in total bilirubin was 16% at Day 7 (n=9) and 41%
at Day 28 (n=8).
- A more detailed description of the preliminary data from the
DUR-928 AH study is provided in a separate press release today and
will be presented during the KOL and earnings call tomorrow at
8:30 a.m. ET.
- About the 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 includes patients with moderate and severe AH (as
determined by initial MELD score). 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 per dose group. The
objectives of this study include assessment of safety, PK and
pharmacodynamic (PD) signals, including liver chemistry, and
biomarkers.
- After completing the low-dose 30 mg cohort (n=4) in moderate AH
patients, the DEC approved commencement of the 90 mg cohort in
moderate AH patients while simultaneously commencing recruitment of
severe AH patients with the 30 mg dose.
- Enrollment of severe AH patients has been more rapid than that
of moderate patients. Upon completion the 30 mg cohort (n=4) in
severe AH patients, the DEC approved advancement to the 90 mg
dosing in severe AH patients. We are now enrolling both moderate
and severe AH patients for the 90 mg cohorts.
- Additional information on the trial design, including
eligibility criteria and site locations, can be found at
www.clinicaltrials.gov using the NCT Identifier NCT03432260.
- In parallel with our ongoing trial, we are supporting Professor
Craig McClain, MD (Chief of Research
Affairs, Division of Gastroenterology, Hepatology and Nutrition,
University of Louisville) in his
efforts to initiate an NIH-funded study of DUR-928 in AH patients
at the University of Louisville.
- AH is a syndrome of progressive inflammatory liver injury
associated with long-term heavy intake of alcohol, and encompasses
a spectrum that ranges from mild injury to severe, life threatening
liver damage. The prevalence of AH is estimated to occur in 10-35%
of heavy drinkers. According to an article in the Journal of
Clinical Gastroenterology (2015 July; 49(6):506-511), there
were over 320,000 hospitalizations related to alcoholic hepatitis
in the U.S. in 2010, resulting in hospitalization costs of nearly
$50,000 per patient. The cost of a
liver transplant exceeds $800,000.
Non-Alcoholic Steatohepatitis (NASH)
- In March 2019 we began enrolling
patients in a Phase 1b randomized and
open-label clinical study being conducted in the U.S. to evaluate
safety, pharmacokinetics and signals of biological activity of
DUR-928 in NASH patients with stage 1-3 fibrosis. Three doses of
DUR-928 (50 mg QD, 150 mg QD and 300 mg BID) will be administered
orally for 28 consecutive days with approximately 20 patients per
dose group for a total of approximately 60 patients in the
trial.
- Key endpoints include safety and pharmacokinetics (PK),
clinical chemistry and biomarkers (e.g., bilirubin, lipids, liver
enzymes, CK-18s, and inflammatory cytokines) as well as liver
imaging (e.g., MRI-PDFF).
- We expect to announce initial data from this study in the
second half of 2019.
- In the Company's previous Phase 1b NASH study, reported at the European
Association for the Study of the Liver (EASL) in April 2017, exploratory biomarker analysis
demonstrated that a single oral dose of DUR-928 in NASH patients,
at both dose levels tested (50 mg and 200 mg), resulted in
statistically significant reductions from baseline of both
full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP
and IL-18.
- Non-alcoholic fatty liver disease (NAFLD) is the most common
form of chronic liver disease in both children and adults. It is
estimated that NAFLD affects about 20% to 30% of adults and 10% of
children in the United States.
NASH, a more severe and progressive form of NAFLD, is one of the
most common chronic liver diseases worldwide, with an estimated
prevalence of more than 10% of adults in the United States, Europe, Japan
and other developed countries. No drug is currently approved for
NAFLD or NASH.
Psoriasis
- We are conducting a Phase 2a, randomized, double-blind,
vehicle-controlled proof-of-concept clinical trial, in which
DUR-928 is applied topically once-daily for four weeks in patients
with mild to moderate plaque psoriasis. The trial is being
conducted at multiple clinical sites in the U.S. Twenty patients
are planned to be enrolled to obtain approximately 15 evaluable
patients. Patients serve as their own controls, applying DUR-928 to
the plaque on one arm and the vehicle to a similar plaque on the
other arm. After the treatment period, patients will be followed
for an additional four weeks. The primary efficacy endpoint is the
change in local psoriasis scores from baseline in the
DUR-928-treated plaques compared to that in the vehicle-treated
plaques. Additional information on the trial design, including
eligibility criteria and site locations, can be found at
www.clinicaltrials.gov using the NCT Identifier 03837743.
- We began enrolling patients in March of 2019 and expect to
announce top line data from this study in the second half of
2019.
- We previously conducted an exploratory Phase 1b trial in psoriasis patients (9 evaluable
patients) in Australia. The trial
was randomized, double-blinded, placebo and self-controlled, using
a micro-plaque assay with intralesional injections of DUR-928. The
results were encouraging and warranted advancing into the current
proof-of-concept trial with topically applied DUR-928. In support
of the Phase 2a study, we have completed multiple non-clinical
safety studies for topically applied DUR-928.
- Psoriasis is an inflammatory skin disease and an
immune-mediated condition that causes the body to make new skin
cells in days rather than weeks. In the
United States, there are about 150,000 new cases of
psoriasis every year and it affects an estimated 7.5 million
Americans. According to the International Federation of Psoriasis
Associations (IFPA), nearly 3% of the world's population has some
form of psoriasis or about 125 million people. Psoriasis causes
itchiness and irritation and may be painful. There's no cure for
psoriasis yet, but currently approved treatment can ease symptoms.
Approximately 80% of patients with psoriasis have localized
disease, which can be treated with topical therapies. As such,
topical agents remain the mainstay of psoriasis treatment.
POSIMIR® (bupivacaine extended-release
solution) Post-Operative Pain Relief Depot. POSIMIR is our
investigational post-operative pain relief depot that utilizes our
patented SABER® technology and is designed to deliver
bupivacaine to provide up to 3 days of pain relief after
surgery.
- After a comprehensive review of the POSIMIR program in light of
the issues raised by the FDA in our communications with them,
including the Complete Response Letter (CRL), we are planning to
submit a full response to the CRL in the second quarter of 2019. As
the submission will be a response to a CRL, we expect a 6-month FDA
review period.
- The effort to evaluate the program, develop a strategy for
filing the response, and the actual writing of key sections of the
response, has been under the direction of Dr. Lee Simon, who was formerly FDA's Division
Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug
Products.
- We believe that the completed inguinal hernia and subacromial
decompression (shoulder) clinical trials support the efficacy of
POSIMIR in post-operative pain and meet the requirements to be
considered as adequate and well-controlled pivotal clinical trials.
Both trials demonstrated a significant decrease in pain and opioid
use over the 0-72 hour period following surgery as compared to
placebo.
- We have completed 16 clinical trials in the POSIMIR program,
involving over 1,400 patients, over 850 of whom received POSIMIR
with the remainder in control groups. We believe this is a
sufficiently sized safety database. We believe that, with the
PERSIST safety data included, we now have sufficient data to
address FDA's issues raised in the CRL and that the data package
meets the requirements for FDA approval.
- POSIMIR has not been approved by the FDA for marketing in the
U.S. for any indication and there can be no assurance that FDA will
approve the planned submission described above.
Indivior Agreement and PERSERIS™. In
September 2017, we entered into a
patent purchase agreement with an affiliate of Indivior PLC,
whereby we assigned certain of its U.S. patent rights to Indivior.
This assignment may provide further intellectual property
protection for PERSERIS (risperidone) extended-release injectable
suspension for the treatment of schizophrenia in
adults.
- Under the terms of the agreement, Indivior has paid us
$12.5 million upfront and a
$5 million milestone based on NDA
approval of PERSERIS. We also receive quarterly earn-out payments
based on a single digit percentage of U.S. net sales for certain
products covered by the patent rights, including PERSERIS. The
patent rights include granted patents extending into at least
2026.
- According to its recent press releases, Indivior has stated
that:
-
- The PERSERIS commercial launch took place in the last week of
February 2019 with a field force of
50 representatives and that modest initial net revenue for Q1 2019
was consistent with their expectations.
- As of February 14, 2019, payor
access was at 38% and Indivior is targeting quality of access
comparable with peers.
- Indivior is targeting appropriate health care providers (HCPs)
with high volume Long Acting Injectables (LAI) practices.
- Indivior plans to focus on key differentiating product specific
attributes, including the first and only once-monthly risperidone
LAI, supplemental oral risperidone or loading dose not recommended,
initial peak plasma concentrations achieved in 4 to 6 hours, and
just one subcutaneous injection monthly.
- Indivior remained confident in its peak year net revenue goal
for PERSERIS of $200 to $300 million.
- U.S. sales of long acting injectables to treat schizophrenia
were in excess of $3 billion in
2017.
- Full prescribing information for PERSERIS, including BOXED
WARNING, and Medication Guide can be found at
www.perseris.com.
Methydur Sustained Release Capsules
(ORADUR®-methylphenidate ER Capsules). In
September 2018, our licensee, Orient
Pharma, informed DURECT that it had obtained marketing
authorization from the Ministry of Health and Welfare in
Taiwan for Methydur Sustained
Release Capsules. This product is indicated for the treatment
of attention deficit hyperactivity disorder (ADHD) and Orient
Pharma has stated that it expects to make Methydur Sustained
Release Capsules commercially available in Taiwan in 2019, while seeking a partner in
China and pursuing regulatory
approvals in selected other countries where it has
commercialization rights and a commercial presence. DURECT retains
rights to North America,
Europe, Japan and all other countries not specifically
licensed to Orient Pharma. DURECT is entitled to receive a
royalty on sales of Methydur Sustained Release Capsules by Orient
Pharma. Orient Pharma has also committed to supply a portion of the
commercial requirements in territories other than the United States for Methydur Sustained
Release Capsules.
Earnings Conference Call
A live audio webcast
of a conference call to discuss first quarter 2019 results and
provide a corporate update will be broadcast live over the internet
at 8:30 a.m. Eastern Time on
May 8, 2019 and is available by
accessing DURECT's homepage at www.durect.com and clicking
"Investors." A replay of the call will be archived on DURECT's
website under Audio Archive 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 Alcoholic Hepatitis (AH) and
acute kidney injury (AKI), 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.
NOTE: ORADUR®, POSIMIR® and
SABER® 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 clinical
development plans for DUR-928, including the ongoing Phase 2a trial
in AH and its preliminary results, the Phase 2a trial in psoriasis
and the Phase 1b trial in patients
with NASH, and the anticipated disclosure of data from clinical
trials, potential future payments from Indivior and Orient Pharma,
potential regulatory approval of POSIMIR, and the potential
benefits and uses of our drug candidates, including the potential
use of DUR-928 to treat acute organ injury such as AH and AKI,
hepatic diseases such as NASH, and inflammatory skin conditions
such as psoriasis and atopic dermatitis, 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 take
longer to conduct than anticipated, do not replicate the results
from earlier clinical or pre-clinical trials, or do not demonstrate
the safety or efficacy of DUR-928 in a statistically significant or
clinically meaningful manner, the risk that the FDA will not
approve POSIMIR, the risk that Indivior's PERSERIS will not obtain
marketplace acceptance, the risk that Orient Pharma will not launch
sales of Methydur Sustained Release Capsules as planned, the risk
that additional time and resources that 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 with
the Securities and Exchange Commission on May 7, 2019 under the heading "Risk Factors."
DURECT
CORPORATION
|
|
CONDENSED
STATEMENTS OF COMPREHENSIVE LOSS
|
(in thousands,
except per share amounts)
|
(unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three months
ended
|
|
|
|
March
31
|
|
|
|
2019
|
|
2018
|
|
|
|
|
|
|
Collaborative
research and development and other revenue
|
|
$
1,500
|
|
$
1,096
|
Product revenue,
net
|
|
2,631
|
|
2,392
|
|
Total
revenues
|
|
4,131
|
|
3,488
|
|
|
|
|
|
|
Operating
expenses:
|
|
|
|
|
|
Cost of product
revenues
|
|
1,136
|
|
1,174
|
|
Research and
development
|
|
6,251
|
|
6,952
|
|
Selling, general and
administrative
|
|
3,454
|
|
3,194
|
Total operating
expenses
|
|
10,841
|
|
11,320
|
|
|
|
|
|
|
Loss from
operations
|
|
(6,710)
|
|
(7,832)
|
|
|
|
|
|
|
Other income
(expense):
|
|
|
|
|
|
Interest and other
income
|
|
209
|
|
158
|
|
Interest and other
expense
|
|
(629)
|
|
(623)
|
Net other
expense
|
|
(420)
|
|
(465)
|
|
|
|
|
|
|
Net loss
|
|
$ (7,130)
|
|
$ (8,297)
|
|
|
|
|
|
|
Net loss per
share
|
|
|
|
|
|
Basic
|
|
$
(0.04)
|
|
$
(0.05)
|
|
Diluted
|
|
$
(0.04)
|
|
$
(0.05)
|
|
|
|
|
|
|
Weighted-average
shares used in computing net loss per share
|
|
|
|
|
|
Basic
|
|
162,091
|
|
153,558
|
|
Diluted
|
|
162,091
|
|
153,558
|
|
|
|
|
|
|
Total comprehensive
loss
|
|
$ (7,134)
|
|
$ (8,297)
|
DURECT
CORPORATION
|
|
CONDENSED BALANCE
SHEETS
|
(in
thousands)
|
|
|
|
|
|
|
|
As of
|
|
As of
|
|
|
March 31,
2019
|
|
December 31,
2018(1)
|
|
|
(unaudited)
|
|
|
ASSETS
|
|
|
|
|
Current
assets:
|
|
|
|
|
Cash and cash equivalents
|
|
$
27,641
|
|
$
31,644
|
Short-term investments
|
|
989
|
|
2,671
|
Accounts receivable
|
|
2,221
|
|
1,757
|
Inventories, net
|
|
3,410
|
|
3,421
|
Prepaid expenses and other current assets
|
|
2,213
|
|
2,247
|
Total current
assets
|
|
36,474
|
|
41,740
|
|
|
|
|
|
Property and
equipment, net
|
|
589
|
|
605
|
Operating lease
right-of-use assets
|
|
7,028
|
|
-
|
Goodwill
|
|
6,399
|
|
6,399
|
Long-term restricted
Investments
|
|
150
|
|
150
|
Other long-term
assets
|
|
1,105
|
|
1,105
|
Total
assets
|
|
$
51,745
|
|
$
49,999
|
|
|
|
|
|
LIABILITIES AND
STOCKHOLDERS' EQUITY
|
|
|
|
|
Current
liabilities:
|
|
|
|
|
Accounts payable
|
|
$
1,933
|
|
$
1,589
|
Accrued liabilities
|
|
4,322
|
|
4,668
|
Contract research liability
|
|
1,489
|
|
1,405
|
Operating lease liabilities, current portion
|
|
1,999
|
|
-
|
Total current
liabilities
|
|
9,743
|
|
7,662
|
|
|
|
|
|
Deferred revenue,
noncurrent portion
|
|
812
|
|
812
|
Term loan, noncurrent
portion, net
|
|
20,670
|
|
20,533
|
Operating lease
liabilities, noncurrent portion
|
|
5,440
|
|
-
|
Other long-term
liabilities
|
|
722
|
|
992
|
|
|
|
|
|
Stockholders'
equity
|
|
14,358
|
|
20,000
|
Total liabilities and
stockholders' equity
|
|
$
51,745
|
|
$
49,999
|
|
(1) Derived
from audited financial statements.
|
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SOURCE DURECT Corporation