Phase IIb Trial Achieves Statistically Significant Reductions in Pain and
Total Consumption of Supplemental Opioid Analgesic Medications Versus Placebo
CUPERTINO, Calif., July 17 /PRNewswire-FirstCall/ — DURECT Corporation
(Nasdaq: DRRX) announced today positive results from a 122 patient Phase IIb
clinical trial of POSIDUR(TM) for treatment of post-operative pain in patients
undergoing inguinal hernia repair. This Phase IIb trial was designed to be the
study upon which DURECT and its collaborator Nycomed would base their decision
for advancing POSIDUR into Phase III clinical trials. In the trial, POSIDUR
demonstrated statistically significant reductions in pain and total
consumption of supplemental opioid analgesic medications versus placebo.
These successful results trigger an $8 million milestone payment to be made by
Nycomed to DURECT under the parties’ collaborative agreement. In preparation
for the Phase III program, DURECT has scheduled an end-of-Phase II meeting
with the U.S. Food and Drug Administration (FDA).
(LOGO: http://www.newscom.com/cgi-bin/prnh/20020717/DRRXLOGO)
“We believe that the results of our Phase IIb trial support the validity
of our POSIDUR product concept of simultaneously relieving pain while reducing
opioid consumption,” stated James Brown, President and CEO of DURECT
Corporation. “Our partnership with Nycomed provides us with financial and
development support along with a strong marketing presence to commercialize
POSIDUR in Europe and other countries. We intend to market POSIDUR ourselves
in the U.S., if approved, thus providing us with a pathway to establishing our
own specialty pharmaceutical business.”
Phase IIb Inguinal Hernia Trial
Design
The POSIDUR Phase IIb clinical trial was designed to evaluate the
tolerability, activity, dose response and pharmacokinetics of POSIDUR in
patients undergoing open inguinal hernia repair. The study was conducted in
Australia and New Zealand as a multi-center, randomized, double blind,
placebo-controlled study in 122 patients. Study patients were randomized into
three treatment groups: patients that were treated with POSIDUR 2.5 mL (n=43),
POSIDUR 5 mL (n=47) and placebo (n=32). The co-primary efficacy endpoints for
the study were Mean Pain Intensity on Movement area under the curve (AUC), a
measure of pain over a period of time, 1-72 hours post-surgery, and the
proportion of patients requiring supplemental opioid analgesic medication
during the study. Secondary efficacy endpoints included Mean Pain Intensity
on Movement AUC over the period 1-48 hours post-surgery, mean total
consumption of supplemental opioid analgesic medication, and time to first use
of supplemental opioid analgesic medication. The threshold for statistical
significance was considered to be at the p<0.05 level.
Results
Pain Control
In relation to the co-primary endpoint of pain reduction as measured by
Mean Pain Intensity on Movement AUC 1-72 hours post-surgery, the patient group
treated with POSIDUR 5 mL reported thirty-one percent (31%) less pain versus
placebo (p=0.0033). A thirty-five percent (35%) reduction of pain as measured
by Mean Pain Intensity on Movement AUC for the period 1-48 hours post-surgery,
a secondary endpoint measure, was reported between the POSIDUR 5 mL treatment
group versus placebo (p=0.0007).
Pain Control
Placebo POSIDUR(TM) % Change p-value
5 mL
Mean Pain Intensity
on Movement AUC (a)
1-72 hours 3.60 2.47 -31% 0.0033 (b)
1-48 hours 3.86 2.52 -35% 0.0007 (b)
(a) Normalized AUC based on a numerical ratings scale for pain intensity
of 0-10, with 0 being no pain.
(b) Using ANCOVA model.
Consumption of Supplemental Opioid Analgesic Medication
Fifty-three percent (53%) of the study patients in the POSIDUR 5 mL group
took supplemental opioid analgesic medications versus seventy-two percent
(72%) of the placebo patients (p=0.0909). Although this positive trend for
this co-primary endpoint in favor of the POSIDUR 5 mL group was not
statistically significant, both secondary endpoints measuring opioid analgesic
medication consumption were met at a statistically significant level. During
the periods of 1-24 hours, 24-48 hours and 48-72 hours after surgery, placebo
patients consumed approximately 3.5 (p=0.0009), 2.9 (p=0.0190) and 3.6
(p=0.0172) times more supplemental opioid analgesic medications (mean total
daily consumption of opioid analgesic medication in morphine equivalents),
respectively, than the POSIDUR 5 mL treatment group. In addition, the median
time to first use of supplemental opioid analgesic medication after surgery
for the placebo patients was 2.7 hours versus >72 hours for the POSIDUR 5 mL
treatment group (p=0.0197).
Consumption of Supplemental Opioid Analgesic Medication
Placebo POSIDUR(TM) % Change Ratio (a) p-value
5 mL
Proportion of
Patients Taking
Supplemental Opioid
Analgesic Medications 72% 53% -26% - 0.0909 (b)
Supplemental Opioid
Analgesic Medications
Taken (c)
1-24 hours 9.24 2.64 -71% 3.5 0.0009 (d)
24-48 hours 4.97 1.70 -66% 2.9 0.0190 (d)
48-72 hours 3.20 0.90 -72% 3.6 0.0172 (d)
Median Time to First
Use of Supplemental
Opioid Analgesic
Medication (hours
post-surgery) 2.7 >72.0 - - 0.0197 (e)
(a) Fold difference between Placebo and POSIDUR(TM) 5 mL.
(b) Using Cochran-Mantel-Haenszel test.
(c) Total mean daily consumption in morphine equivalents.
(d) Using ANCOVA model.
(e) Using Log-Rank test for comparison of Kaplan-Meier survival curves.
Dose Finding
POSIDUR administered at the dose of 5 mL showed statistically significant
activity relative to placebo whereas POSIDUR administered at 2.5 mL showed a
positive trend relative to placebo on certain parameters but the results were
not statistically significant. DURECT intends to select POSIDUR 5 mL as the
dose to use in the Phase III program.
Safety
The patient groups treated with POSIDUR 5 mL and POSIDUR 2.5 mL showed
comparable safety profiles as the patient groups treated with placebo, and the
drug administration appeared well tolerated. The side effects commonly
observed with opioid medication use were less frequent in the POSIDUR 5 mL and
2.5 mL treatment groups compared to placebo.
Other Exploratory Phase II studies
In addition to the Phase IIb study described above, DURECT has also been
conducting smaller exploratory Phase II studies in hernia, shoulder
arthroscopy and appendectomy surgeries to evaluate different application
techniques, clinical design and conduct as well as other investigational
factors. These trials have been conducted in multiple cohorts, generally
consisting of approximately 6-21 patients in each treatment group. Hernia and
shoulder studies have been completed while an appendectomy study is on-going.
In all the exploratory studies, patient groups treated with POSIDUR 5 mL and
POSIDUR 2.5 mL showed comparable safety profiles as the patient groups treated
with placebo, and the drug administration appeared well tolerated. Some
treatment groups from the hernia and shoulder exploratory studies utilizing
POSIDUR have shown positive activity as measured by reduction of pain or
consumption of supplemental opioid analgesic medication versus placebo, while
other treatment groups have not. We are continuing to evaluate these studies
to understand the different results observed, and intend to apply our
learnings in the design of our Phase III program.
Conference Call Information
DURECT Corporation will be hosting a conference call to discuss this
announcement on July 17, 2007 at 11:00 AM Eastern Time / 8:00 AM Pacific Time.
To participate in the conference call, please dial in to (800) 254-0499
(domestic) or (408) 960-7131 (international) and request the “DURECT Corporate
Event,” entry code 5020. Please dial in 10 minutes prior to the scheduled
start time. An audio rebroadcast will be available one hour after the
conference ends for 24 hours. The replay dial-in number within the US is
1-800-642-1687 (Reservation #: 7221981). The international replay dial-in
number is 1-706-645-9291. The conference call is also available live over the
Internet at http://www.www.durect.com.
About POSIDUR
POSIDUR is a long-acting local anesthetic under development by DURECT and
Nycomed for the treatment of post-surgical pain. It is intended to be
administered during surgery, where it continuously releases therapeutic levels
of bupivacaine in a controlled fashion, providing up to 72 hours of
uninterrupted local analgesia. POSIDUR’s performance is due to DURECT’s
patented SABER(TM) delivery system, an injectable, biodegradable drug delivery
technology.
About the DURECT / NYCOMED Collaboration
In November 2006, DURECT signed a collaboration agreement with Nycomed, a
privately-held European pharmaceutical company headquartered in Switzerland,
whereby the companies are jointly developing DURECT’s POSIDUR post-operative
pain relief depot. Under the terms of the agreement, Nycomed paid DURECT an
upfront license fee of $14 million; with the payment of the $8 million
clinical development milestone described above, DURECT may earn additional
milestone payments of up to $180 million due upon achievement of additional
defined development, regulatory and sales milestones. The two parties are
jointly directing and equally funding a development program for POSIDUR
intended to secure regulatory approval in both the U.S. and the European Union
(E.U.). DURECT has licensed Nycomed the exclusive commercialization rights to
POSIDUR in the E.U. and select other countries. In addition, DURECT will
manufacture and supply the product to Nycomed for commercial sale in the
territory licensed to Nycomed. Nycomed will pay DURECT blended royalties on
sales in the defined territory of 15-40% depending on annual sales, as well as
a manufacturing mark-up. DURECT retains full ownership of POSIDUR in the
U.S., Canada, Asia and other countries.
About DURECT Corporation
DURECT Corporation is an emerging specialty pharmaceutical company
developing pharmaceutical systems based on its proprietary drug delivery
platform technologies. The Company currently has a number of late-stage
pharmaceutical products in development addressing large markets in pain
management, with a number of research programs underway targeting chronic
disease and other therapeutic areas. For more information, please visit
http://www.www.durect.com.
DURECT Forward-Looking Statement
The statements in this press release regarding POSIDUR, its potential
performance and attributes, our anticipated end-of-Phase II meeting with the
FDA and future development plans for POSIDUR and our intended emergence as a
specialty pharmaceutical company 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, Nycomed and our abilities to
design, enroll, conduct and complete clinical trials, obtain successful
results from such clinical trials, complete the design, development, and
manufacturing process development of POSIDUR, obtain regulatory and
manufacturing approvals from regulatory agencies, and manufacture and
commercialize POSIDUR, as well as marketplace acceptance of POSIDUR. Further
information regarding these and other risks is included in DURECT’s Form 10-Q
dated May 9, 2007 under the heading “Risk Factors.”
NOTE: POSIDUR(TM) and SABER(TM) are trademarks of DURECT Corporation.
POSIDUR is under development and has not been submitted or approved for
commercialization by the FDA or other health authorities.
SOURCE DURECT Corporation
07/17/2007
CONTACT: Matthew J. Hogan, Chief Financial Officer of DURECT
Corporation, +1-408-777-4936; or media, Jeremiah Hall, Senior Vice President
of Feinstein Kean Healthcare, +1-415-677-2700, jeremiah.hall@fkhealth.com, for
DURECT Corporation
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Web site: http://www.www.durect.com