Top-line Data Demonstrate Primary Endpoint Achieved in Final Pivotal Phase 3 Study of Sufentanil NanoTab PCA System For

 Top-line Data Demonstrate Primary Endpoint Achieved in Final Pivotal Phase 3
 Study of Sufentanil NanoTab PCA System For Management of Post-Operative Pain

- Following major orthopedic surgery, Sufentanil NanoTab-treated patients
experienced significantly greater reduction in pain as measured by SPID-48 vs.
placebo (p<0.001) -

- Results confirm all previously reported Phase 3 trial outcomes, supporting
submission of an NDA anticipated for third quarter 2013 -

- AcelRx to conduct conference call and webcast today, May 21, 8:30 a.m. EDT
(5:30 a.m. PDT) -

PR Newswire

REDWOOD CITY, Calif., May 21, 2013

REDWOOD CITY, Calif., May 21, 2013 /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 demonstrating that
in a placebo-controlled Phase 3 study of its investigational sublingual
Sufentanil NanoTab PCA (patient-controlled analgesia) System (NanoTab System),
the primary efficacy endpoint was achieved. The study evaluated control of
pain intensity compared to baseline during the 48-hour study period
immediately following major orthopedic surgery, specifically knee or hip
replacement, using the FDA-requested primary endpoint of Summed Pain Intensity
Difference to baseline (i.e. SPID-48). Results demonstrated that patients
receiving sufentanil NanoTabs realized a significantly greater SPID-48 during
the study period than placebo-treated patients (+76.1 vs -11.5, p<0.001).
Secondary endpoint data showed that SPID at 24 hours and 72 hours was also
significantly greater in the sufentanil-treated patients than in the
placebo-treated patients (p<0.001 in each case). Adverse events reported in
the study were generally mild or moderate in nature and were similar in both
placebo and treatment groups for the majority of adverse events.

"With the successful completion of this study, AcelRx has now achieved
positive results in all three Phase 3 studies in which the Sufentanil NanoTab
PCA System has been evaluated," said Richard King, president and CEO of
AcelRx. "We remain on track for a third quarter 2013 NDA submission for the
NanoTab System, a product which, if approved, will present AcelRx with an
opportunity to fundamentally redefine the management of post-operative pain
for tens of millions of patients both in the U.S. and around the world."

Phase 3 Orthopedic Study Design and Demographics

Utilizing a randomized, double-blind, placebo-controlled design, this pivotal
Phase 3 study enrolled 426 adult patients at 34 U.S. sites for treatment of
moderate=to-severe acute pain immediately following major orthopedic surgery.
Seven patients did not receive study drug, resulting in 419 patients being
included in the intent-to-treat (ITT) population. Patients were treated for a
minimum of 48 hours, and up to 72 hours. Patients were randomized 3:1, with
315 patients randomized to sufentanil treatment and 104 to placebo treatment.
Both treatments were delivered by the patient, as needed, using the NanoTab
System with a 20-minute lock-out period. Patients in both groups could
receive up to 2 mg morphine intravenously per hour as a rescue medication, the
primary purpose of this rescue medication being to enable placebo-treated
patients to stay in the study. Pain scores recorded just prior to the
delivery of rescue medication were gathered and imputed forward to minimize
the impact of this rescue opioid on efficacy evaluations.

As with our other Phase 3 studies, there was no upper limit on age or weight
in recruitment of patients in this study. The oldest patient treated was 90
years of age, the heaviest had a BMI of 62 kg/m^2. Historically, older
patients are more susceptible to the adverse events caused by opioids, and
heavier patients tend to have greater risk of obstructive apnea, which is
often worsened by opioids. This should allow the regulatory agency to review
data for treating these two at-risk groups with sufentanil. Overall, patient
demographics (percentage of patients) in this study were as follows:

                                                  BMI (kg/m^2) <30: Age (yrs)
           Male: Female Caucasian: Non-Caucasian >30
                                                                     <65: >65
Sufentanil 40:60        85:15                     54:46              41:59
Placebo    37:63        87:13                     50:50              48:52

Primary Endpoint Data

Two hundred fifteen (68.3%) sufentanil NanoTab-treated patients completed the
48-hour study period, compared to 43 (41.3%) placebo-treated patients.
Primary reasons for drop-out in the sufentanil- and placebo-treated groups
were adverse events (7.0% and 6.7%, respectively) and lack of efficacy (14.3%
and 48.1%, respectively). The primary endpoint measure, SPID-48, was +76.1
for sufentanil-treated patients and -11.5 for placebo-treated patients
(p<0.001).

Key Secondary Endpoint Data
SPID separated between sufentanil- and placebo-treated patients after the
first hour, and was highly significant at all timepoints thereafter as
illustrated below.

Group                  SPID-24 SPID-48 SPID-72
Sufentanil NanoTab     33.8    76.1    166.2
Placebo                -8.8    -11.5   -2.6
Statistical Comparison P<0.001 P<0.001 P<0.001

A secondary endpoint focused on Total Pain Relief measured at 48 hours
(TOTPAR-48) was significantly higher in the sufentanil-treated patients than
in the placebo-treated patients (p<0.001). In addition, another secondary
endpoint, measurement of Patient Global Assessment with Method of Pain Control
at 48 hours (PGA-48) was also highly significant in favor of
sufentanil-treated patients (p<0.001).

Safety and Tolerability Profile

Treatment-emergent adverse events were generally mild to moderate in nature
and similar for the majority of adverse events between sufentanil and placebo
treated patients, despite the shorter duration of exposure in the
placebo-treated patients caused by early termination due to inadequate
analgesia. Adverse events of nausea (occurring in 52.7% of sufentanil-treated
patients vs 33.7% of placebo-treated patients), vomiting (12.7% vs 5.8%,
respectively), dizziness (6% vs 1%, respectively) and itching (6% vs 0%,
respectively) were the only adverse effects that statistically separated
between sufentanil- and placebo-treated patients. Nausea, vomiting and
itching are common in treatment of post-operative patients, and are easily
managed with anti-emetic and anti-histamine treatment. Effective management
of these symptoms is demonstrated by the low drop-out rate due to nausea (1.6%
of sufentanil-treated patients vs 2.9% of placebo-treated patients), vomiting
(0.6% vs 0%, respectively) and itching (0.3% vs 0%, respectively) in this
study. Two patients (one each in the sufentanil group and placebo group)
experienced a serious adverse event considered possibly or probably related to
the study drug by the investigator.

Dr. Pamela Palmer, chief medical officer for AcelRx and an anesthesiologist
said, "My primary concern with the use of opioids in the treatment of
moderate-to-severe pain, especially in the elderly, is respiratory events.
Each of the two Phase 3 pivotal studies has shown no statistical difference
between sufentanil- and placebo- treated patients for any respiratory event.
In addition, our Phase 3 head-to-head study demonstrated statistically fewer
patients with oxygen desaturation events with sufentanil NanoTab than IV PCA
morphine based on pulse oximetry monitoring."

Dr. David Griffin, an orthopedic surgeon at the Orthopaedic Center of Vero
Beach, the first site to enroll in this study, said "The Sufentanil NanoTab
PCA System eliminates the risk of programming errors and frees the patient
from an IV connection which facilitates patient ambulation. These advantages,
coupled with the excellent efficacy and safety of this System that we have
observed in our study patients, should lead to better patient satisfaction and
better patient outcomes."

Summary of Previously Reported Phase 3 Data

This study is the last of 3 successful Phase 3 studies conducted by AcelRx to
support U.S. and ex-US regulatory review of the Sufentanil NanoTab PCA
System. In November 2012, AcelRx announced positive top-line results for the
NanoTab System in a Phase 3 open-label, active-comparator study evaluating the
efficacy and safety of the NanoTab System compared to IV PCA with morphine
(study IAP-309) in the management of moderate-to-severe acute pain after
surgery. Results from this study demonstrated that the NanoTab System met its
primary endpoint of non-inferiority in patient global assessment (PGA), with
method of pain control in comparison to IV PCA with morphine at 48 hours.
Additional analyses also demonstrated that the NanoTab System was
statistically superior to IV PCA morphine for the PGA measurement. In
addition, 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 using a
validated assessment questionnaire. Further analyses of results from this
study, presented at the ASRA meeting in May 2013 demonstrated that sufentanil
delivered via the NanoTab System had a significantly greater pain intensity
reduction in the first four hours after starting treatment than IV PCA
morphine. In addition, there were fewer patients throughout the study that
experienced oxygen desaturation events below 95% in the NanoTab System group
than in the IV PCA morphine group. Oxygen saturation is a measure of a
patient's respiratory function and can be affected negatively by opioids. A
decrease in oxygen saturation can be linked to the serious adverse event of
respiratory depression.

In March 2013, the company announced top-line results from a randomized,
double-blind, placebo-controlled, pivotal Phase 3 study evaluating the ability
of sufentanil NanoTabs delivered by the NanoTab System to control
moderate-to-severe acute pain after major abdominal surgery compared to
placebo (study IAP-310). Results demonstrated that patients receiving
sufentanil NanoTabs realized a significantly greater SPID-48 during the study
period than placebo-treated patients. Secondary endpoint data also showed that
24 hours and 72 hours after first dose, SPID was significantly greater in the
sufentanil-treated patients than in the placebo-treated patients. Results
from this study, when combined with results from the orthopedic study
announced today, meet the requirements defined by the FDA to submit an
application for a broad label to manage post-operative pain in the hospital
setting.

A comparison of efficacy measures below, including SPID-48, TOTPAR-48 and
percent of patients reporting "good" or "excellent" PGA-48 demonstrates the
consistency of effect using the NanoTab System across the various patient
populations studied in Phase 3 (major abdominal and major orthopedic surgery
patients):

Study                SPID-48 TOTPAR-48 PGA-48
IAP-309 - Abdominal  108.2   102.4     81.1%
IAP-309 – Orthopedic 79.6    99.8      77.9%
IAP-310 – Abdominal  105.6   93.3      67.8%
IAP-311 – Orthopedic 76.5    91.3      70.2%

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
U.S. and EU, with an additional 27 million procedures in countries with
moderate to high per capita healthcare expenditures. The U.S., 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 the Sufentanil NanoTab PCA System

The NanoTab System 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
NanoTab System is designed to address the limitations of IV PCA by offering:

  oA high therapeutic index opioid: NanoTab System 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.
  oA non-invasive route of delivery: The sublingual route of delivery used by
    the NanoTab System provides rapid onset of analgesia, therefore reducing
    the risk of IV-related analgesic gaps and IV complications, such as
    catheter-related infections. In addition, because patients are not
    physically connected via IV tubing to a pump for pain relief, the NanoTab
    System allows for ease of patient mobility.
  oA simple, pre-programmed PCA solution: NanoTab System is pre-programmed
    that eliminates the risk of pump programming errors by the healthcare
    providers.

Conference Call

AcelRx will conduct a conference call and webcast today, May 21, 2013, at 8:30
a.m. Eastern time (5:30 a.m. Pacific time) to discuss the orthopedic
postoperative pain Phase 3 top-line results. To listen to the conference
call, dial in approximately ten minutes before the scheduled call to
1-800-860-2442 for domestic callers, 1-866-605-3852 for Canadian callers, or
1-412-858-4600 for international callers. Those interested in listening to
the conference call live via the Internet may do so by visiting the
Investors/Upcoming Events 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 Investors 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 Sufentanil NanoTab PCA System, 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 complexity of
infusion pumps. The NanoTab System has successfully completed all three of
its planned Phase 3 clinical trials and a New Drug Application submission is
planned for the third quarter of 2013. AcelRx has announced positive top-line
results for a Phase 2 trial for ARX-04, a sufentanil formulation for the
treatment of moderate-to-severe acute pain, funded through a grant from U.S.
Army Medical Research and Materiel Command. The company has two additional
pain treatment product candidates, ARX-02 and ARX-03, which have completed
Phase 2 clinical development. 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 of the top-line clinical data in the final pivotal Phase 3 study
of NanoTab System, the potential submission of an NDA for NanoTab System and
the timing thereof, therapeutic and commercial potential of NanoTab System 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
possibility that subsequent analyses of the data 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; any delays or inability to obtain and maintain
regulatory approval of its product candidates in the United States and Europe;
its ability to attract funding partners or collaborators with development,
regulatory and commercialization expertise; its ability to obtain sufficient
financing to complete registration of its product candidates in the United
States and Europe; the market potential for its product candidates; 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 filed with the SEC on March 8, 2013. 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.

(Logo: http://photos.prnewswire.com/prnh/20130226/MM67303LOGO)

SOURCE AcelRx Pharmaceuticals, Inc.

Website: http://www.acelrx.com
Contact: Jim Welch, Chief Financial Officer, AcelRx Pharmaceuticals, Inc.,
+1-650-216-3511
 
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