CUPERTINO, Calif., March 7, 2019 /PRNewswire/ -- DURECT
Corporation (Nasdaq: DRRX) today announced financial results for
the three months and year ended December 31,
2018 and provided a corporate update.
- Total revenues were $3.6 million
and net loss was $7.3 million for the
three months ended December 31, 2018
as compared to total revenues of $19.5
million and net profit of $8.2
million for the three months ended December 31, 2017. Revenues for the three months
ended December 31, 2017 included the
recognition of $15.4 million in
deferred revenue from the $20 million
upfront fee associated with our terminated agreement with Sandoz
AG.
- Total revenues were $18.6 million
and net loss was $25.3 million for
the year ended December 31, 2018,
compared to total revenues of $49.2
million and net loss of $3.7
million for the year ended December
31, 2017. Revenues for the year ended December 31, 2018 included a $5 million milestone payment from Indivior
related to the NDA approval of PERSERIS™ (risperidone); revenues
for the year ended December 31, 2017
included a $20 million upfront fee
from Sandoz AG and a $12.5 million
upfront payment from Indivior.
- At December 31, 2018, cash and
investments were $34.5 million,
compared to cash and investments of $36.9
million at December 31, 2017.
Debt at December 31, 2018, including
partial accrual for the final payment of our term loan, was
$20.5 million.
"Based on encouraging data from both of the completed moderate
and severe alcoholic hepatitis (AH) 30 mg cohorts, the relatively
rapid enrollment of severe AH patients, and strong encouragement
from several of our key expert advisors and clinical trial
investigators, we have decided to continue our AH trial by
conducting the next cohort of severe AH patients at the 90 mg dose.
In parallel, we are continuing to recruit patients in the moderate
AH 90 mg cohort and work with Dr. McClain at the University of Louisville on enabling initiation of
his NIH-funded DUR-928 AH trial. We also look forward to generating
and reporting data this year from the NASH and psoriasis trials in
which patients will receive daily doses of DUR-928 for 28 days,"
stated James E. Brown, D.V.M.,
President and CEO of DURECT. "In addition, we will be
requesting approval of POSIMIR when we submit to the FDA a full
response to the Complete Response Letter. If successful, this could
lead to FDA approval this year. Also, Indivior announced that
the commercial launch of PERSERIS in the U.S. took place in
February 2019. We receive quarterly
earn-out payments on U.S. net sales of PERSERIS."
Potential milestones in 2019:
- Reporting initial data from a DUR-928 multi-dose trial in NASH
patients
- Reporting top-line data from a DUR-928 Phase 2a
proof-of-concept trial in mild to moderate plaque psoriasis
patients
- Completing the 90 mg cohort in severe AH patients
- Submission to and acceptance by the FDA of a full response to
the CRL for POSIMIR and potential NDA approval following an
expected six-month review period
- Commercial launch of PERSERIS by Indivior in the U.S.
- Commercial launch of Methydur by Orient Pharma in Taiwan
- New license and collaboration agreements
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 several hepatic and renal 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
Non-Alcoholic Steatohepatitis (NASH)
- This will be an open-label, Phase 1b study conducted in the U.S. to evaluate
safety, pharmacokinetics and signals of biological activity of
DUR-928 in patients with NASH. Three doses of oral DUR-928 (low,
middle and high) will be administered daily for 28 consecutive
days. We plan to enroll approximately 20 patients per dose group
for a total of approximately 60 patients in the trial. We expect to
begin enrolling patients during the first quarter of 2019 and
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.
Alcoholic Hepatitis (AH)
- DURECT is conducting a Phase 2a clinical trial with
intravenously administered DUR-928 in patients with alcoholic
hepatitis (AH). This is an open label, dose escalation,
multi-center U.S. study, originally designed to be conducted in two
sequential parts. Part A includes patients with moderate AH (as
determined by the Model of End-Stage Liver Disease (MELD) scores, a
common scoring system to assess the severity and prognosis of AH
patients), and Part B includes patients with severe AH. Three dose
levels (30, 90 and 150 mg) were planned for testing in Part A. 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 biochemistry
and biomarkers.
- After completing dosing for the low-dose 30 mg cohort (n=4) of
Part A (moderate AH patients), the DEC approved commencement of the
90 mg cohort in Part A while simultaneously commencing recruitment
for Part B (severe AH patients) with the 30 mg dose.
- We have now completed dosing of the 30 mg cohort (n=4) of Part
B, the enrollment of which was much more rapid than Part A. After
reviewing the safety and PK data, the DEC has approved commencement
of the 90 mg cohort in Part B. Based on the encouraging data from
both the moderate and severe 30 mg cohorts, the relatively rapid
enrollment of severe AH patients, and strong encouragement from
several of our key expert advisors and clinical trial
investigators, we have decided to continue our trial by conducting
the next cohort of severe AH patients at the 90 mg dose.
- In parallel with our recruitment of patient for both of the 90
mg cohorts in our trial, we are supporting Dr. Craig McClain's efforts to initiate his
NIH-funded study 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
2010, resulting in hospitalization costs of nearly $50,000 per patient.
Psoriasis
- In this Phase 2a, randomized, double-blind, vehicle-controlled
proof-of-concept clinical trial, DUR-928 will be applied topically
once-daily for four weeks in patients with mild to moderate plaque
psoriasis. The trial will be conducted at multiple clinical sites
in the U.S. Twenty patients are planned to be enrolled to obtain
approximately 15 evaluable patients. Patients will 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 will be the change in local psoriasis
scores from baseline in the DUR-928-treated plaques compared to
that in the vehicle-treated plaques. We expect to begin enrolling
patients during the first quarter of 2019 and announce top line
data from this study in the second half of 2019. Additional
information on the trial design, including eligibility criteria and
site locations, can be found at www.clinicaltrials.gov using the
NCT Identifier 03837743.
- The Company 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, the Company has
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 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 the
Company's investigational post-operative pain relief depot that
utilizes the Company's 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 first half 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, the Company entered into a patent
purchase agreement with an affiliate of Indivior PLC, whereby the
Company 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 the Company
$12.5 million upfront and a
$5 million milestone based on NDA
approval of PERSERIS. The Company also receives 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.
- Through press releases on December 18,
2018, and February 14 and 27,
2019, Indivior has stated that:
-
- PERSERIS was made available in the U.S. in late November 2018.
- The PERSERIS commercial launch took place in February 2019 with a field force of 50
representatives.
- 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.
Debt Amendment. In November
2018, the Company amended its existing $20 million term loan with Oxford Finance such
that principal payments now commence 18 months later than
previously scheduled (i.e., commencing June
1, 2020 rather than December 1,
2018) and the final maturity date is moved back by 30 months
(i.e., from August 1, 2020 to
November 1, 2022). The interest
rate and final payment remain unchanged, and the Company paid
Oxford Finance an amendment fee of $900,000.
Earnings Conference Call
A live audio webcast
of a conference call to discuss fourth quarter 2018 and year ended
December 31, 2018 results and provide
a corporate update will be broadcast live over the internet at
4:30 p.m. Eastern Time on
March 7 and is available by
accessing DURECT's homepage at www.durect.com and clicking
"Investor Relations." A replay of the call will be archived on
DURECT's website under Audio Archive in the "Investor Relations"
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 approved in July 2018. 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 continuation of the Phase
2a trial in AH, plans for a Phase 2a trial in psoriasis and a 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 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, 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
when anticipated, 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 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 on November 8, 2018
under the heading "Risk Factors."
DURECT
CORPORATION
|
|
CONDENSED
STATEMENTS OF COMPREHENSIVE LOSS
|
(in thousands,
except per share amounts)
|
(unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three months
ended
|
|
Twelve months
ended
|
|
|
December
31
|
|
December
31
|
|
|
2018
|
|
2017
|
|
2018
|
|
2017
|
|
|
|
|
|
|
|
|
|
Collaborative
research and development and other revenue
|
$
775
|
|
$16,273
|
|
$
8,207
|
|
$23,577
|
Product revenue,
net
|
2,852
|
|
3,265
|
|
10,357
|
|
13,093
|
Revenue from sale of
intellectual property rights
|
-
|
|
-
|
|
-
|
|
12,500
|
|
Total
revenues
|
3,627
|
|
19,538
|
|
18,564
|
|
49,170
|
|
|
|
|
|
|
|
|
|
Operating
expenses:
|
|
|
|
|
|
|
|
|
Cost of product
revenues
|
1,093
|
|
1,061
|
|
4,263
|
|
6,633
|
|
Research and
development
|
5,887
|
|
6,604
|
|
25,501
|
|
31,609
|
|
Selling, general and
administrative
|
3,539
|
|
3,303
|
|
12,419
|
|
13,165
|
Total operating
expenses
|
10,519
|
|
10,968
|
|
42,183
|
|
51,407
|
|
|
|
|
|
|
|
|
|
Income (loss) from
operations
|
(6,892)
|
|
8,570
|
|
(23,619)
|
|
(2,237)
|
|
|
|
|
|
|
|
|
|
Other income
(expense):
|
|
|
|
|
|
|
|
|
Interest and other
income
|
238
|
|
287
|
|
870
|
|
967
|
|
Interest and other
expense
|
(645)
|
|
(622)
|
|
(2,573)
|
|
(2,425)
|
Net other
expense
|
(407)
|
|
(335)
|
|
(1,703)
|
|
(1,458)
|
|
|
|
|
|
|
|
|
|
Net income
(loss)
|
$ (7,299)
|
|
$
8,235
|
|
$(25,322)
|
|
$ (3,695)
|
|
|
|
|
|
|
|
|
|
Net income (loss) per
share
|
|
|
|
|
|
|
|
|
Basic
|
$
(0.05)
|
|
$
0.06
|
|
$
(0.16)
|
|
$
(0.03)
|
|
Diluted
|
$
(0.05)
|
|
$
0.05
|
|
$
(0.16)
|
|
$
(0.03)
|
|
|
|
|
|
|
|
|
|
Weighted-average
shares used in computing net income (loss) per share
|
|
|
|
|
|
|
|
|
Basic
|
162,040
|
|
149,428
|
|
159,834
|
|
145,273
|
|
Diluted
|
162,040
|
|
150,759
|
|
159,834
|
|
145,273
|
|
|
|
|
|
|
|
|
|
Total comprehensive
income (loss)
|
$ (7,299)
|
|
$
8,234
|
|
$(25,321)
|
|
$ (3,693)
|
DURECT
CORPORATION
|
|
CONDENSED BALANCE
SHEETS
|
(in
thousands)
|
|
|
|
|
|
As of
|
|
As of
|
|
December 31,
2018
|
|
December 31,
2017(1)
|
|
(unaudited)
|
|
|
ASSETS
|
|
|
|
Current
assets:
|
|
|
|
Cash and cash equivalents
|
$
31,644
|
|
$
29,375
|
Short-term investments
|
2,671
|
|
7,384
|
Accounts receivable
|
1,757
|
|
2,376
|
Inventories, net
|
3,421
|
|
3,163
|
Prepaid expenses and other current assets
|
2,247
|
|
3,060
|
Total current
assets
|
41,740
|
|
45,358
|
|
|
|
|
Property and
equipment, net
|
605
|
|
929
|
Goodwill
|
6,399
|
|
6,399
|
Long-term restricted
Investments
|
150
|
|
150
|
Other long-term
assets
|
1,105
|
|
277
|
Total
assets
|
$
49,999
|
|
$
53,113
|
|
|
|
|
LIABILITIES AND
STOCKHOLDERS' EQUITY
|
|
|
|
Current
liabilities:
|
|
|
|
Accounts payable
|
$
1,589
|
|
$
1,520
|
Accrued liabilities
|
4,668
|
|
5,511
|
Contract research liability
|
1,405
|
|
834
|
Deferred revenue, current portion
|
-
|
|
682
|
Term loan, current portion, net
|
-
|
|
7,281
|
Total current
liabilities
|
7,662
|
|
15,828
|
|
|
|
|
Deferred revenue,
noncurrent portion
|
812
|
|
1,093
|
Term loan, noncurrent
portion, net
|
20,533
|
|
13,578
|
Other long-term
liabilities
|
992
|
|
1,126
|
|
|
|
|
Stockholders'
equity
|
20,000
|
|
21,488
|
Total liabilities and
stockholders' equity
|
$
49,999
|
|
$
53,113
|
|
(1) Derived
from audited financial statements.
|
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SOURCE DURECT Corporation