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:
- Zalviso 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".
- A 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.
- Secondary 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:
- A 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.
- A 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.
- A 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.