AcelRx Pharmaceuticals Submits New Drug Application to the FDA for Zalviso™

 AcelRx Pharmaceuticals Submits New Drug Application to the FDA for Zalviso™

Zalviso NDA submitted for the management of moderate-to-severe acute pain in
adult patients in the hospital setting

PR Newswire

REDWOOD CITY, Calif., Sept. 30, 2013

REDWOOD CITY, Calif., Sept. 30, 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 that it submitted a New Drug
Application (NDA) to the U.S. Food and Drug Administration (FDA) for Zalviso™
(sufentanil sublingual microtablet system). Zalviso is a patient-activated,
non-invasive analgesic system, which delivers 15 mcg sufentanil per dose as
needed for pain control, subject to a 20 minute lockout period between doses.
The proposed indication for Zalviso is the management of moderate-to-severe
acute pain in adult patients in the hospital setting. The NDA submission is
based primarily on data from a Phase 3 registration program that included two
double-blind randomized placebo-controlled clinical trials, one conducted in
patients following major abdominal surgery, the other in patients following
major joint replacement surgery. Additionally, a Phase 3 open-label
active-comparator trial was conducted in patients following either major
abdominal or orthopedic surgery, comparing Zalviso to the current standard of
care, intravenous patient-controlled analgesia (IV PCA) with morphine.
Zalviso successfully achieved the primary efficacy endpoints for each of
these studies. Treatment-emergent adverse events were typical of opioid usage
post-operatively, were generally mild-to-moderate in nature, and were similar
in both active- and placebo-treatment groups for the majority of adverse
events.

"The Zalviso NDA submission represents a major milestone for AcelRx as we seek
FDA approval for our first product candidate based on our proprietary
sublingual sufentanil formulation and our delivery system technology," stated
Richard King, president and CEO of AcelRx. "Based on the results of our
clinical trials, we believe Zalviso has demonstrated an ability to achieve
rapid onset of pain relief, thereby enabling patients to manage their
moderate-to-severe acute pain effectively over 48 to 72 hours post-surgery.
If approved by the FDA, Zalviso could provide hospitals and patients with an
attractive alternative to the current standard of care, specifically IV
PCA-delivered opioids."

The NDA submission required payment to the FDA of a $1.95 million NDA filing
fee in the third quarter of 2013, which will be included in the Company's
income statement as an additional research and development expense. FDA
regulations allow for the waiver of the NDA filing fee if the Company is
filing its first NDA and qualifies as a small business with less than 500
employees. The FDA requested the Small Business Administration (SBA) to
determine if AcelRx was a small business, and the SBA recently ruled that
AcelRx could not qualify as a small business.

Previously Reported Phase 3 Clinical Trial Results for Zalviso

The 505(b)(2) NDA submission for Zalviso is based on a comprehensive
development program and includes data from AcelRx's three Phase 3 clinical
trials. As previously reported, Zalviso met the FDA-agreed primary endpoints
in the two double-blind, placebo-controlled Phase 3 registration studies
conducted in patients who had undergone major open-abdominal surgery or
orthopedic surgery that involved either knee or hip replacement procedures.
In each of these trials, patients treated with Zalviso to manage their
post-surgical pain reported a greater sum of the pain intensity difference to
baseline over 48 hours (SPID-48) compared to placebo-treated patients (p=0.001
and p<0.001, respectively). Adverse events considered possibly or probably
related to treatment were generally mild-to-moderate in nature and similar for
the majority of adverse events between Zalviso- and placebo-treated patients,
with the exception of itching, which was significantly greater (p < 0.05) in
the Zalviso-treated group.

The third Phase 3 study, an open-label, active-comparator trial comparing
Zalviso to IV PCA with morphine demonstrated that:

  oZalviso was non-inferior (p<0.001) to IV PCA morphine based on the primary
    endpoint of Patient Global Assessment of method of pain control comparison
    over the 48-hour trial period (PGA48) as determined by the combined
    percentage of patients with PGA ratings of "good" or "excellent".
  oA secondary comparison of the primary endpoint demonstrated that Zalviso
    was statistically superior to IV PCA morphine for the PGA48 endpoint
    (p=0.007). Statistically superior and non-inferior PGA comparisons for
    Zalviso compared to IV PCA morphine were also seen at the 24-hour and
    72-hour time points.
  oSecondary endpoints of summed pain intensity, summed pain relief, and
    dropouts due to inadequate analgesia over the 48-hour study period were
    similar between treatment groups.

Zalviso had a significantly faster reduction in pain intensity compared to IV
PCA morphine in the first 4 hours of treatment. Fewer patients experienced
oxygen desaturation events below 95% in the Zalviso-treated group compared to
the IV PCA morphine-treated patients (p=0.028). In addition, both nurses and
patients rated Zalviso significantly higher for Overall Satisfaction and Ease
of Care compared to IV PCA with morphine. Overall, adverse events in the
comparison trial were similar and most were mild-to-moderate in nature in both
treatment groups.

About Zalviso

Zalviso is an investigational pre-programmed, non-invasive, handheld system
that allows hospital patients with moderate-to-severe acute pain to self-dose
with sublingual sufentanil microtablets to manage their pain. Zalviso is
designed to address the limitations of IV PCA by offering:

  oA high therapeutic index opioid - Zalviso uses the high therapeutic index
    opioid sufentanil. It offers hospitalized adult patients with
    moderate-to-severe acute pain 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 Zalviso provides rapid onset of analgesia, and also eliminates the risk
    of IV-related analgesic gaps and IV complications, such as
    catheter-related infections in IV PCA treated patients. In addition,
    because Zalviso patients do not require direct connection to an IV PCA
    infusion pump through IV tubing, Zalviso allows for ease of patient
    mobility.
  oA simple, pre-programmed PCA solution – Zalviso is a pre-programmed PCA
    system designed to eliminate the risk of infusion pump programming errors.

About Moderate-to-Severe Acute Pain

Moderate-to-severe acute pain management in the hospital remains a challenge
for healthcare providers with up to 75% of patients reporting inadequate pain
relief following surgery. Inadequate treatment of moderate-to-severe 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. Approximately 12 million
surgical procedures per year result in moderate-to-severe pain in the U.S.,
with an additional 7.4 million hospital inpatients in the U.S. annually
experiencing moderate-to-severe acute pain from other, non-post surgical,
medical conditions. Currently, patients experiencing moderate-to-severe acute
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 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,
Zalviso™, 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. AcelRx
has announced positive results from each of the three Phase 3 clinical trials
for Zalviso and has submitted an NDA to the FDA seeking its approval. AcelRx
has also 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 the 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 therapeutic benefits of Zalviso, the
process and timing of anticipated future clinical development of AcelRx
Pharmaceuticals' product candidates, the commercial potential of Zalviso and
the anticipated timing and therapeutic and commercial potential of AcelRx
Pharmaceuticals' other 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 fact
that FDA may not accept for filing Zalviso NDA; ability to obtain regulatory
approval for Zalviso, including whether the results of the Phase 3 clinical
trials for Zalviso are sufficient to obtain marketing approval for Zalviso,
which depends on the ability of AcelRx to demonstrate to the satisfaction of
the FDA the safety and efficacy of Zalviso based upon its findings of the
Phase 3 trials; 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 from 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; resolution
of the determination of AcelRx Pharmaceutical's status as a small business by
SBA; 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 filed with the SEC on August 12, 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, 650.216.3511, jwelch@acelrx.com
 
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