AcelRx Pharmaceuticals Announces ANESTHESIOLOGY® 2022 Annual Meeting Presentation on DSUVIA® for Battlefield Analgesia by the Uniformed Services University of the Health Sciences

Presentation concludes that future battlefield medicine efforts should focus on newer analgesics like DSUVIA® across military settings and establish protocols for their implementation in the trauma setting

HAYWARD, Calif., Oct. 25, 2022 /PRNewswire/ -- AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), (AcelRx), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings, today announced that an abstract entitled, "Evolution Of Opioid Analgesia On The Battlefield For Moderate-to-Severe Acute Pain" (abstract # A4123) was presented by lead author, Sharon Kim, M.S., at the ANESTHESIOLOGY® 2022 annual meeting, held October 21-25, 2022 in New Orleans, LA. The authors of the abstract, from the nation's federal health sciences university, recommend the adoption of a sufentanil sublingual tablet (SST), 30 mcg (or DSUVIA®) by the Department of Defense (DoD) to improve pain management in the battlefield setting.

In the abstract, the authors state, "In 2018, the DoD introduced its newest synthetic opioid, sublingual sufentanil tablet (SST), intended to be a more effective analgesic option" noting that SST is the first oral mucosal opioid microtablet (3mm diameter) designed to provide analgesia within as early as 15 minutes from administration, maintain therapeutically effective analgesic levels for up to 3 hours, and reduce the risk of dosing errors through its innovative applicator design. The authors then highlight that "the sublingual tablet  has a bioadhesive surface to adhere to the oral mucosa, minimizing salivary response and swallowing" and state that the "sublingual administration enables a longer drug plasma half-life allowing for more consistent plasma concentrations over time and eliminating the need for repeated dosing. Since sublingual sufentanil has a high therapeutic index with no active metabolites, drug administration incurs minimal side-effects (e.g., nausea, dizziness, headache) and is not associated with cognitive impairment." The therapeutic index of a drug is the margin of safety that exists between the dose of a drug that produces the desired effect and the dose that produces unwanted and possibly dangerous side effects.

The authors continued by noting that, in contrast to morphine and fentanyl, sublingual sufentanil has minimal euphoric effects that commonly drive opioid addiction. In particular, the authors identified the combination of the tablet formulation and sublingual delivery of the SST provides a low peak drug plasma concentration, thus avoiding the initial high peak opioid concentrations responsible for adverse events.  The authors acknowledged that "to date, no transmucosal opioid products are approved for the treatment of moderate-to-severe acute pain in patients who are opioid-naive, demonstrating the medical benefits of SSTs."

The authors concluded, "Overall, the DoD recognizes the therapeutic benefits of potent opioids in acute trauma settings and has aimed to improve battlefield opioid usage, which evolved from IV morphine administration to [fentanyl] lollipops to finally SSTs. Future work should aim to improve opioid products for the battlefield, discover non-opioid analgesic options, and establish optimal drug administration protocol in trauma settings."

"DSUVIA offers an alternative for pain relief with many potential advantages for use on the battlefield including ease of dosing, rapid onset and a high therapeutic index," stated Vince Angotti, Chief Executive Officer of AcelRx. As the military acknowledges, DSUVIA is the only transmucosal opioid that is approved for patients who are opioid-naive, such as our soldiers in the military. The Department of Defense, or DoD, has repeatedly recognized the need for a product like DSUVIA, a novel sublingual tablet which they believe should provide a safer alternative to our soldiers for pain relief compared to existing options. We continue to work with the critical decision-makers at the Department of Defense to make this important drug available to our men and women serving in our U.S. military."

E-Abstracts will be presented virtually and made available to registrants throughout the entire meeting from Saturday, October 22 (7:00 a.m. US Central Time) through Tuesday, October 25, 2022 (3:00 p.m. U.S. Central Time). The abstracts will remain available and open to meeting attendees for three months after the meeting.

History of Pain Management in the Military Setting
Morphine has been the primary analgesic on the battlefield since the 19th century and was originally developed as a less addictive alternative to opium. However, the drug has a narrow therapeutic index (TI), and morphine abuse and overdose continued into World War II and the 20th century. Even after the inception of morphine over a century ago, the U.S. military has used intramuscular (IM) morphine for battlefield analgesia, although disadvantages include inconsistent absorption, delayed onset, and compromised pain relief. In 1996, the Department of Defense (DoD) developed the Tactical Combat Casualty Care (TCCC) guidelines for trauma life support and pain management in prehospital combat settings. The 1996 TCCC guidelines stated that IV morphine is preferable to IM morphine due to the more rapid onset of action, providing faster pain relief and decreasing the risk for overdose. The DoD then shifted focus to introducing opioids that can be administered through the oral or nasal mucosa when IV access is unfeasible. In 2004, the DoD added oral transmucosal fentanyl citrate (OTFC) to the TCCC guidelines. OTFC was primarily used to treat intense cancer pain but was recommended for off-label use on the battlefield. OTFC is packaged as a lozenge on a handle (like a lollipop) and quickly absorbed through the oral mucosa. Some fentanyl that is swallowed is absorbed through the gastrointestinal tract. Disadvantages of OTFC include a high incidence of side-effects (nausea, vomiting, respiratory depression, sedation) and risk for opioid addiction and misuse.¹

About DSUVIA (sufentanil sublingual tablet), 30 mcg
DSUVIA®, known as DZUVEO® in Europe, is indicated for use in adults in certified medically supervised healthcare settings, such as hospitals, surgical centers, and emergency departments, for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. DSUVIA was designed to provide rapid analgesia via a non-invasive route and to eliminate dosing errors associated with intravenous (IV) administration. DSUVIA is a single-strength, solid dosage form administered sublingually via a single-dose applicator (SDA) by healthcare professionals. Sufentanil is an opioid analgesic previously only marketed for IV and epidural anesthesia and analgesia. The sufentanil pharmacokinetic profile, when delivered sublingually, avoids the high peak plasma levels and short duration of action observed with IV administration. DZUVEO has been approved by the European Medicines Agency and AcelRx's European commercialization partner, Aguettant, will market the drug in Europe.

This release is intended for investors only.  For more information, including important safety information and black box warning for DSUVIA, please visit www.DSUVIA.com.

About AcelRx Pharmaceuticals, Inc.
AcelRx Pharmaceuticals, Inc. is a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for use in medically supervised settings. AcelRx's proprietary, non-invasive sublingual formulation technology delivers sufentanil with consistent pharmacokinetic profiles. The Company has one approved product in the U.S., DSUVIA® (sufentanil sublingual tablet, 30 mcg), approved as DZUVEO® in Europe, indicated for the management of acute pain severe enough to require an opioid analgesic for adult patients in certified medically supervised healthcare settings, and several product candidates. The Company's product candidates include: two developmental pre-filled, ready-to-use syringes of ephedrine and phenylephrine licensed for the U.S. from Aguettant; Niyad™, a developmental device for use as a regional anticoagulant for the extracorporeal circuit; LTX-608, for the potential treatment of COVID-19, disseminated intravascular coagulation, acute respiratory distress syndrome and acute pancreatitis; and Zalviso® (sufentanil sublingual tablet system, SST system, 15 mcg), an investigational product in the U.S. being developed as an innovatively designed patient-controlled analgesia (PCA) system for reduction of moderate-to-severe acute pain in medically supervised settings.

This release is intended for investors only. For additional information about AcelRx, please visit www.acelrx.com.

About Uniformed Services University of the Health Sciences
The Uniformed Services University (USU) of the Health Sciences, founded by an act of Congress in 1972, is the nation's federal health sciences university and the academic heart of the Military Health System. USU students are primarily active-duty uniformed officers in the Army, Navy, Air Force and Public Health Service who receive specialized education in tropical and infectious diseases, TBI and PTSD, disaster response and humanitarian assistance, global health, and acute trauma care. USU also has graduate programs in oral biology, biomedical sciences and public health committed to excellence in research. The University's research program covers a wide range of areas important to both the military and public health. For more information about USU and its programs, visit www.usuhs.edu.

About the ANESTHESIOLOGY 2022 Annual Meeting
The ANESTHESIOLOGY Annual Meeting is the marquee annual event for the American Society of Anesthesiologists®. Founded in 1905, the American Society of Anesthesiologists is an educational, research and scientific association of physicians organized to raise the standards of the medical practice of anesthesiology and to improve patient care. As of 2021, the organization included more than 55,000 national and international members.

References
¹ Kim, Sharon, et al. "Evolution Of Opioid Analgesia On The Battlefield For Moderate-to-Severe Acute Pain" Abstract A4123 – ANESTHESIOLOGY 2022, New Orleans, LA.

Forward-Looking Statements
This press release contains forward-looking statements, including, but not limited to, statements related to the potential adoption and benefits of DSUVIA for use in military settings. These and any other forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking terminology such as "potential," "believe," "offer", "expect," "expected," "anticipate," "may," "will," "should," "seek," "approximately," "intends," "plans," "estimates," "benefits," or the negative of these words or other comparable terminology. The discussion of financial trends, strategy, plans or intentions may also include forward-looking statements, which are predictions, projections and other statements about future events that are based on current expectations and assumptions. These forward-looking statements involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied by such statements, including:  (i) risks relating to AcelRx's product development activities and ongoing commercial business operations; (ii) risks related to the ability of AcelRx to implement its development plans, forecasts and other business expectations; (iii) risks related to unexpected variations in market growth and demand for AcelRx's commercial and developmental products and technologies; and (iv) risks relating to AcelRx's ability to obtain regulatory approvals for its developmental product candidates. Although it is not possible to predict or identify all such risks and uncertainties, they may include, but are not limited to, those described under the caption "Risk Factors" and elsewhere in AcelRx's annual, quarterly and current reports (i.e., Form 10-K, Form 10-Q and Form 8-K) as filed or furnished with the Securities and Exchange Commission (SEC) and any subsequent public filings. You are cautioned not to place undue reliance on any such forward-looking statements, which speak only as of the date such statements were first made. To the degree financial information is included in this press release, it is in summary form only and must be considered in the context of the full details provided in AcelRx's most recent annual, quarterly or current report as filed or furnished with the SEC. AcelRx's SEC reports are available at www.acelrx.com under the "Investors" tab. Except to the extent required by law, AcelRx undertakes no obligation to publicly release the result of any revisions to these forward-looking statements to reflect new information, events or circumstances after the date hereof, or to reflect the occurrence of unanticipated events.

SOURCE AcelRx Pharmaceuticals, Inc.