DSUVIA™ (formerly ARX-04)

-SOO-vee-ə

DSUVIA (in US)
  • Pre-Clinical
  • Phase 1
  • Phase 2
  • Phase 3
  • NDA Filed
  • Approved
ARX-04 (in EU)
  • Pre-Clinical
  • Phase 1
  • Phase 2
  • Phase 3
  • MAA Filed
  • Approved

 

Moderate-to-Severe Acute Pain in Trauma and Ambulatory Care Settings

In situations of trauma or injury, it is advantageous to have a rapid-acting, non-invasive method for treating acute pain. In the battlefield, emergency medicine and ambulatory care environments, patients may not have immediate intravenous (IV) access available. Intramuscular (IM) injections are the current standard of care on the battlefield11, but they are invasive, painful, and have been rated less effective than IV opioids at providing fast pain relief.2 In cases of severe trauma where the patient is often in hypovolemic shock and muscles are not well perfused, pain medication given by intramuscular injection may not readily reach the blood stream to provide pain relief, rendering this route of delivery suboptimal.3 Additionally, IV dosing results in high peak plasma levels, thereby limiting the amount of opioid that can be used at once, and requiring frequent re-dosing to titrate to satisfactory analgesia. Moreover, oral pills and liquids have generally shown slower and more erratic onset of analgesia in comparison to IV administration.4

DSUVIA Potential Settings of Use

DSUVIA (sufentanil sublingual tablet, 30 mcg) is an investigational product candidate consisting of 30 mcg sufentanil in very small sublingually absorbed tablets that are delivered via a disposable, pre-filled, single-dose applicator (SDA). AcelRx is developing DSUVIA for the management of moderate-to-severe acute pain in a variety of medically supervised settings, including in emergency medicine, outpatient or ambulatory surgery, non-surgical patients experiencing pain in the hospital, or post-operative patients, following short-stay surgery, who do not require more long-term analgesia.

DSUVIA Market Opportunity

In the United States, AcelRx anticipates the moderate-to-severe acute pain market would be comprised of four heathcare settings: the emergency services (emergency departments and pre-hospital emergency medicine); certain hospital procedures, including out-patient or short-stay in-patient surgeries; painful procedures performed in-office; and ambulatory surgical centers. The Healthcare Cost and Utilization Project (HCUP) reports that 111.8 million adults utilize the emergency services annually, of whom it is estimated that more than 51 million experienced moderate-to-severe acute pain5 An estimated 105.5 million adult patients enter the hospital setting for out-patient and short-stay in-patient procedures, 5.1 million of whom experience moderate-to-severe acute pain, according to the American Hospital Association.6 In-office and ambulatory surgery centers combined treat another 68.2 million adults, 8.8 million of whom experience moderate-to-severe acute pain.7,8Based on an analysis of the above market segments, AcelRx estimates that the market potential of DSUVIA in the U.S. is expected to be approximately $1.1 billion.

Current Development Status

In September 2016, AcelRx completed the ARX-04 Phase 3 clinical program, which is comprised of three Phase 3 studies:

SAP301: a multi-center, double-blind, placebo-controlled Phase 3 trial in patients with moderate-to-severe acute pain following ambulatory abdominal surgery. AcelRx reported in September 2015 that DSUVIA met primary and secondary endpoints in this study. Results of SAP301 demonstrated that patients receiving DSUVIA experienced significantly greater pain reduction compared to placebo, as measured by the time-weighted Summed Pain Intensity Difference to baseline over the first 12 hours of treatment (SPID-12) (p<0.001).12 Adverse events reported in the study were typical of opioid therapy and were similar for patients treated with DSUVIA and placebo, the most common of which were nausea, headache and vomiting.

SAP302: a multi-center, open-label Phase 3 trial of DSUVIA for the treatment of adult patients who present to the emergency department with moderate-to-severe acute pain associated with trauma or injury. SAP302 enrolled patients in two cohorts: 1) 40 adults who were administered a single dose of DSUVIA; and 2) 36 adults who were eligible to receive up to four doses of DSUVIA, given hourly as needed for pain. Overall, the 76 adults treated with DSUVIA in this study experienced a mean pain intensity difference to baseline (PID) of 2.9 on a 0-10 numeric rating scale at 60 minutes.13 Patients treated in the first cohort experienced a mean decrease from baseline of 2.7 after a single dose of DSUVIA14; and patients in the second cohort reported a mean decrease from baseline of 3.113. DSUVIA showed 79% of patients reporting no adverse events, with the most commonly reported adverse events being nausea (9%), somnolence (5%) and vomiting (4%). A cognitive impairment assessment using the validated Six-Item Screener was also conducted within SAP302, and demonstrated that DSUVIA was not associated with drug-induced cognitive impairment.13.

SAP303: a multi-center, open-label Phase 3 trial for the treatment of moderate-to-severe acute pain in patients who had undergone short-stay in-patient or out-patient surgery. SAP303 enrolled 140 patients aged ≥40 years, 17% of whom where aged ≥65 years and 29% of whom had baseline renal and/or hepatic impairment. In this study, treatment with DSUVIA was associated with improvements in pain intensity as early as 30 minutes after the start of DSUVIA dosing, a 49% reduction in mean pain intensity from baseline (from 6.19 to 3.17 on a 0-10 numeric rating scale) during the first 2 hours, and maintenance of that reduction for the duration of the 12-hour study period. Safety results showed the most frequently reported adverse events in the total population were nausea (27%) and headache (6%). Overall, safety and efficacy findings were similar among patients regardless of age and renal or liver function.15

AcelRx filed a New Drug Application for DSUVIA for the treatment of moderate-to-severe acute pain in medically supervised settings with the U.S. Food and Drug Administration (FDA) in December 2016.

DSUVIA development is funded in part by the U.S. Army Medical Research and Materiel Command (USAMRMC) under contract No. W81XWH-15-C-0046.

NOTE: DSUVIA is pronounced: -SOO-vee-ə

 

  1. Gandy J. Ketamine in Tactical Combat Casualty Care. Defense Health Board Decision Briefing, Trauma and Injury Subcommittee, February 2012
  2. Thomas, SL and Shewakramani, S. Prehospital Trauma Analgesia. Journal of Emergency Medicine 2008; 35(1): 47-57
  3. de Moya, M. A. Shock. In Merck manual online, professional version. Retrieved from (link)
  4. Cashman, J. Routes of Administration. In Macintyre, P.E., Rowbotham, D.J., and Walker, S.M., Clinical Pain Management Second Edition: Acute Pain, Volume 1 (pp. 205). Taylor & Francis Group, LLC, Oct 26, 2012
  5. Nationwide Emergency Department Sample (NEDS) 2009-2011.
  6. National Survey of Ambulatory Surgery (NSAS) 2006.
  7. In-house commissioned market research. ZS Associates "Opportunity Assessment, US & EU" August 2014.
  8. In-house commissioned market research. Millennium Research Group " US Market Opportunity Study for Sublingual Sufentanil" March 2010.
  9. Data on File. In-house commissioned market research. Quintiles® “ARX04: Asset forecast for Europe” Study dated May 3, 2016*
  10. Guéant, S, et al. Quality of Pain Management in the Emergency Department: Results of a Multicentre Prospective Study. European Journal of Anaesthesiology 2011; 28(2): 97–105
  11. New Drugs Online Report for Methoxyflurane. 2016. Uk Medicines Information. (link)
  12. Minkowitz H, Lakshman S, Leiman D et al. Safety and Efficacy of Sufentanil Sublingual 30 mcg Tablets for the Treatment of Acute Pain following Outpatient Abdominal Surgery. Presentation at the American Society of Anesthesiologists Annual Meeting, October 2015, San Diego, CA

  13. Palmer P. Phase 3 Efficacy and Safety Results of Sufentanil Sublingual Tablet. Presentation at 2016 Military Health System Research Symposium.
  14. Hassan JR, Miner J, Minkowitz H, DiDonato K, Palmer P. Phase 3 Efficacy and Safety Results of Sufentanil Sublingual 30mcg Tablet for Management of Acute Traumatic Pain in Emergency Medicine. Presentation at the 7th World Congress of Mountain & Wilderness Medicine.
  15. AcelRx (2016). AcelRx Reports Positive Safety and Efficacy Results for ARX-04 (sufentanil sublingual tablet 30 mcg) in Elderly Patients and Patients with Hepatic Impairment in Third Phase 3 Registration Trial, SAP303 [Press Release]