AcelRx Announces Primary Endpoint Met in Phase 3 Non-Inferiority
Study of Sublingual Sufentanil NanoTab® PCA System vs. IV PCA
Morphine for Post-Operative Pain
REDWOOD CITY, Calif.,
Nov. 15, 2012 /PRNewswire/ -- AcelRx
Pharmaceuticals, Inc. (Nasdaq: ACRX), a specialty pharmaceutical
company focused on the development and commercialization of
innovative therapies for the treatment of acute and breakthrough
pain, today announced top-line data showing that the open-label
Phase 3 study of its investigational sublingual (under the tongue)
Sufentanil NanoTab PCA (patient-controlled analgesia) System met
its primary endpoint of non-inferiority in patient global
assessment (PGA) with method of pain control in comparison to
intravenous (IV) PCA with morphine. Additional analyses also
showed that in this study the NanoTab System was statistically
significantly superior to IV morphine for the PGA measurement.
In addition, using validated assessment tools, nurses
managing patients in the study and the patients themselves reported
that they had significantly greater Overall Satisfaction with the
NanoTab System compared to IV PCA morphine and significantly
greater Overall Ease of Care with the NanoTab System compared to IV
PCA morphine.
"With these impressive top-line results from this head-to-head
clinical trial, we have successfully completed an important step
towards our New Drug Application (NDA) submission and, dependent on
completing the remaining Phase 3 trials and obtaining FDA approval,
eventual commercialization of the Sufentanil NanoTab PCA System,"
commented Richard King, President
and CEO, of AcelRx Pharmaceuticals, Inc. "Delivering
patient-controlled analgesia in a non-invasive, pre-programmed
system that provides powerful pain control while enhancing patient
ease of care and satisfaction and nurse satisfaction compared to
current invasive delivery systems will be a major advance for
hospital care."
Utilizing a randomized, open-label, parallel-group design, this
Phase 3 study enrolled 359 adult patients at 26 U.S. sites and
compared efficacy and safety of AcelRx's investigational ARX-01
sublingual Sufentanil NanoTab PCA System (15 mcg/dose) to the
commonly used IV PCA with morphine (1 mg/dose) for the treatment of
acute post-operative pain immediately following major abdominal or
orthopedic surgery. Patients were randomized 1:1 to treatment
with the NanoTab System or IV PCA morphine and were treated for
post-operative pain for a minimum of 48 hours and up to 72
hours.
Top-line results of the Phase 3 clinical trial demonstrate that
the Sufentanil NanoTab PCA System was non-inferior (p<0.001) to
IV PCA morphine for the primary endpoint of PGA over the 48-hour
study period as determined by the combined percentage of patients
with PGA ratings of "good" or "excellent" (78.5% vs. 66.1%
respectively). The assessment of non-inferiority is based on
a lower limit of -15% for the 95% confidence interval (CI) around
the difference between these percentages. Because the 95% CI
was +3.2% to +21.6% for the 48 hour PGA and therefore didn't cross
the zero difference line, a statistical analysis for superiority
could be performed, which demonstrated that for this study, the
NanoTab System was statistically superior to IV PCA morphine for
the PGA endpoint (p=0.009). This statistically superior PGA
was also seen at the 24 hour and 72 hour timepoints.
Additionally, the percentage of patients rating the NanoTab System
as "Excellent" was higher than those rating IV PCA morphine as
excellent (42.9% vs. 30.6%, p=0.016). Similar percentages of
NanoTab System-treated and IV PCA morphine-treated patients dropped
out of the study prematurely due to lack of efficacy (7.3% vs. 8.3%
respectively) or due to an adverse event (7.9% vs. 11.1%
respectively).
Nurses setting up the different treatments for use and managing
patients in the study reported that they had greater Overall
Satisfaction (3.93 vs. 3.32 out of 5, p<0.001) and Overall Ease
of Care (4.26 vs. 3.82, p=0.018) with the Sufentanil NanoTab PCA
System compared to IV PCA morphine. Likewise, patients in the
study reported that they had greater Overall Satisfaction (4.15 vs.
3.83 out of 5, p=0.003) and greater Overall Ease of Care (4.45 vs.
4.07, p<0.001) with the NanoTab System compared to IV PCA
morphine.
"Our goal at AcelRx has always been to improve upon the
management of post-operative pain using a simplified system that
nurses don't have to program," commented Pamela Palmer MD, PhD, Chief Medical Officer and
AcelRx co-founder. "The validated Patient Overall Ease of
Care assessment is a multi-dimensional evaluation that includes
confidence, comfort and ease of movement with the delivery device,
along with dosing confidence, pain control and knowledge and
understanding of product use. The higher score in this
composite measure, which reflects higher scores in each of the
subscales, along with the higher nursing Overall Satisfaction
ratings, and combined with the excellent pain control demonstrated
in the PGA rating validates our efforts for developing this product
for hospitalized patients" added Dr. Palmer.
"It was impressive to observe the ease of set-up and use of the
Sufentanil NanoTab PCA System by both nurses and patients compared
to our typical IV PCA system," stated study investigator Dr.
Harold Minkowitz in the Department
of Anesthesiology at Memorial-Hermann Hospital in Houston, Texas. "Observing the rapid
onset and significant level of pain relief obtained with this
non-invasive route of opioid administration over a broad range of
patients and types of surgery was remarkable."
In addition to this well-controlled supportive trial, two other
Phase 3 clinical studies of the Sufentanil NanoTab PCA System are
underway. In March 2012, AcelRx
initiated a randomized, double-blind, placebo-controlled efficacy
and safety study comparing the NanoTab System to placebo for
post-operative pain control following major open abdominal
surgery. In August 2012, AcelRx
initiated a randomized, double-blind, placebo-controlled efficacy
and safety study comparing the NanoTab System to placebo in
treating post-operative pain following major joint replacement
surgery. Data from both of these pivotal studies are expected
in the first quarter of 2013. Additional information about
the Phase 3 clinical trials with the NanoTab System can be found by
visiting www.clinicaltrials.gov and using the identifiers,
NCT01660763, NCT01539642 and NCT01539538.
About Post-Operative Pain
Acute pain management in
the hospital, in particular post-operative analgesia, remains a
challenge for healthcare providers with up to 75% of patients
reporting inadequate pain relief following surgery.
Inadequate treatment of post-surgical pain can lead to
decreased mobility, which increases the risks for serious medical
complications, including deep vein thrombosis and partial lung
collapse, potentially resulting in extended hospital stays.
More than 30 million surgical procedures per year result in
moderate to severe pain in the US and EU, with an additional 27
million procedures in countries with moderate to high per capita
healthcare expenditures. The US, 5 main EU countries and
Japan represented $5.1 billion of acute pain treatment product
sales in 2008. Currently patients experiencing post-operative pain
in the hospital may have IV PCA treatment, typically utilizing
morphine or hydromorphone. However, there are deficiencies
associated with the current use of IV PCA that can negatively
impact patient safety, well-being and recovery. These include
drug-related side effects associated with morphine or
hydromorphone, complications associated with IV delivery, and
medication delivery errors typically associated with misprogramming
of the complex IV PCA pumps.
About ARX-01, the Sufentanil NanoTab PCA System
ARX-01 is an investigational pre-programmed, non-invasive,
handheld system that allows post-operative patients to self-dose
with sublingual Sufentanil NanoTabs to manage their post-operative
pain. The ARX-01 System is designed to address the
limitations of IV PCA by offering:
- A high therapeutic index opioid: ARX-01
uses the high therapeutic index opioid sufentanil; it offers
post-operative pain patients the potential for effective
patient-controlled analgesia with a low incidence of drug-related
side effects.
- A non-invasive route of delivery: The sublingual route
of delivery used in ARX-01 provides rapid onset of analgesia,
therefore eliminating the risk of IV-related analgesic gaps and IV
complications, such as catheter-related infections. In
addition, because patients are not tethered to IV tubing and a pump
for pain relief, ARX-01 allows for ease of patient mobility.
- A simple, pre-programmed PCA solution: ARX-01 is a
pre-programmed PCA System designed to eliminate the risk of pump
programming errors.
Conference Call
The conference call and webcast will be held today, Thursday, November 15, 2012 at 8:00 a.m. Eastern Time (5:00 a.m. Pacific Time) to discuss the Phase 3
top-line results. To listen to the conference call, dial in
approximately ten minutes before the scheduled call to (800)
860-2442 for domestic callers, (866) 605-3852 for Canadian callers,
or (412) 858-4600 for international callers. Those interested
in listening to the conference call live via the Internet may do so
by visiting the Investor Relations section of the company's website
at www.acelrx.com.
A webcast replay will be available on the AcelRx website for 90
days following the call by visiting the Investor Relations section
of the company's website at www.acelrx.com
About AcelRx Pharmaceuticals, Inc.
AcelRx Pharmaceuticals, Inc. is a specialty pharmaceutical
company focused on the development and commercialization of
innovative therapies for the treatment of acute and breakthrough
pain. AcelRx's lead product candidate, the ARX-01 Sufentanil
NanoTab PCA System, which is currently in Phase 3 clinical
development, is designed to solve the problems associated with
post-operative intravenous patient-controlled analgesia which has
been shown to cause harm to patients following surgery because of
the side effects of morphine, the invasive IV route of delivery and
the inherent potential for programming and delivery errors
associated with the complexity of infusion pumps. AcelRx has
two additional product candidates which have completed Phase 2
clinical development: ARX-02 for the treatment of cancer
breakthrough pain, and ARX-03 for mild sedation, anxiety reduction
and pain relief for patients undergoing painful procedures in a
physician's office. AcelRx has initiated a Phase 2 study for
a fourth product candidate, ARX-04, a sufentanil formulation for
the treatment of moderate-to-severe acute pain, funded through a
grant from the U.S. Army Medical Research and Materiel Command, or
USAMRMC. For additional information about AcelRx's clinical
programs please visit www.acelrx.com.
Forward Looking Statements
This press release contains forward-looking statements,
including, but not limited to, statements related to the process
and timing of anticipated future clinical development of AcelRx
Pharmaceuticals' product candidates, including the release ARX-01
top-line clinical trial data, the release and anticipated timing of
additional ARX-01 clinical trial data, the potential filing of an
NDA for the ARX-01 and the timing thereof, therapeutic and
commercial potential of ARX-01 and the anticipated timing and
therapeutic and commercial potential of other AcelRx
Pharmaceuticals' product candidates. These forward-looking
statements are based on AcelRx Pharmaceuticals' current
expectations and inherently involve significant risks and
uncertainties. AcelRx Pharmaceuticals' actual results and the
timing of events could differ materially from those anticipated in
such forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks related to:
the ability of AcelRx Pharmaceuticals to successfully complete the
clinical trials for ARX-01, that fact that subsequent analyses of
the full data set may lead to different (including less favorable)
interpretations of the results than the analyses conducted to date
or may identify important implications of the study that are not
reflected in these statements, or be subject to differing
interpretations by the regulatory agencies; the success, cost
and timing of all product development activities and clinical
trials; the uncertain clinical development process, including the
risk that clinical trials, have an effective design, enroll a
sufficient number of patients, or be completed on schedule, if at
all; any delays or inability to obtain regulatory approval of its
product candidates in the United
States and Europe; its
ability to obtain adequate clinical supplies of the drug and device
components of its product candidates; its ability to attract
funding partners or collaborators with development, regulatory and
commercialization expertise; its ability to obtain sufficient
financing to complete development and registration of its product
candidates in the United States
and Europe; its ability to obtain
and maintain regulatory approvals of its product candidates in
the United States and Europe; the market potential for its product
candidates; the accuracy of AcelRx Pharmaceuticals' estimates
regarding expenses, capital requirements and needs for financing;
and other risks detailed in the "Risk Factors" and elsewhere in
AcelRx Pharmaceuticals' U.S. Securities and Exchange Commission
filings and reports, including its Quarterly Report on Form 10-Q
for the three months ended September
30, 2012. AcelRx Pharmaceuticals undertakes no duty or
obligation to update any forward-looking statements contained in
this release as a result of new information, future events or
changes in its expectations.
SOURCE AcelRx Pharmaceuticals, Inc.