Battlefield Pain Management
Battlefield pain management focuses on safely and effectively treating pain at, or very close to the point-of-injury. Pain treatments must work quickly, be safe, easy-to-use and lightweight to allow medics to carry sufficient doses for the planned operation. Our new products meet these requirements and add to the pain-treatment options available to care providers.
The objective of BPM-KET is to achieve FDA approval of the current anesthetic ketamine product as an analgesic and field a ketamine analgesic that can be used by Warfighters. As a rapid acting non-opioid medication, ketamine will treat acute pain close to the point of injury (tactical field care, tactical evacuation care, and Role 1). Ketamine will allow safe analgesia, even with repeated use during prolonged field care and prolonged evacuation times.
Battlefield pain management is a key focus for the DOD, which must improve the delivery of pain relief at, or as close as possible to, the point-of-injury in both space and time. The alleviation of pain caused by a traumatic battlefield injury significantly improves the potential for Soldier survival, favorable functional outcomes, and is an essential element of patient care in any situation. Good options for the combat medic are increasingly limited as the morphine sulfate auto-injector is no longer available nor accepted as the standard of care, having been found ineffective in multiple cases of treatment of severe wounds. The current alternative, Oral Transmucosal Fentanyl Citrate, is also suffering from limited availability, and is approved only for use in chronic pain syndromes found in cancer patients. It is specifically labeled not to be used for acute pain management, which is how it is being used in theater. Both of these opioids have serious side effects, including respiratory and cardiovascular suppression, as well as the risk of overuse, addiction, diversion and abuse.
Ketamine was approved in 1970 as an anesthetic for intravenous or intramuscular administration. Its analgesic properties have long-been recognized, both alone, and more commonly in combination with other analgesics. Established effects of ketamine, beyond the primary analgesic effect, make it particularly valuable for battlefield pain management. It has hypnotic (sedative/sleep-producing) and amnesic effects coupled with a lack of impact on airway reflexes, respiratory function, and sympathomimetic cardiovascular effects (increased arterial pressure and heart rate). Additionally, ketamine appears to minimize early wind-up and suppress central sensitization with acute pain, reduce the likelihood of N-Methyl-D-aspartic acid (NMDA) receptor mediated neuroplasticity, and limit or prevent opioid hyperalgesia. Preliminary evidence suggests utility in the treatment of drug resistant depression and PTSD, with a potential benefit of preventing or reducing PTSD.
Emergent Biosolutions, Inc. (EBSI) completed a clinical and non-clinical literature review and submitted it to the FDA as part of a Pre-Investigational New Drug application meeting (Pre-IND) to gain concurrence on expanding the label with already available data (i.e. without a clinical trial). The FDA responded that the data in literature is not enough, and that a clinical trial would be needed to expand the label indication. EBSI completed a draft of the clinical protocol and this has been reviewed by USAMMDA.
The MS B brief is planned for fiscal year 2021.
Sufentanil NanoTab® (DSUVIA™) (BM-SUFNT)
The Sufentanil® Nanotab (DSUVIA™) system is an alternative battlefield pain management product that is safe, fast-acting and administered without the necessity of starting an IV or intraosseous infusion. Developed by AcelRx Pharmaceuticals, the system consists of sufentanil sublingual microtablets dispensed by a Licensed Health Care Provider in a proprietary dispenser, for treatment of acute pain management.
The relief of severe pain associated with traumatic injury is a key element of treatment far forward on the battlefield, as well as at every level in the continuum of care. In addition to the obvious humanitarian need to spare patients unnecessary suffering, pain is also associated with disruptions of physiology, difficulties with patient management, and even with the incidence of Post-Traumatic Stress Disorder (PTSD). The alleviation of pain caused by a traumatic battlefield injury significantly improves the potential for service member survival and favorable functional outcomes, and it is an essential element of patient care in any situation. The currently fielded material solution, intramuscular morphine sulfate delivered by an auto-injector, has significant drawbacks regarding both effectiveness and safety. The commonly used alternative, Oral Transmucosal Fentanyl Citrate, presents significant risks of overuse and diversion, and is licensed only for use in chronic pain syndromes found in cancer patients. It is specifically labeled not to be used for acute pain management, which is how it is being used in theater.
AcelRx resubmitted an NDA to the FDA on May 8, 2018. The FDA's Anesthetic and Analgesic Drug Products Advisory Committee voted 10-3 in support of NDA approval on October 12, 2018, and the FDA subsequently approved DSUVIA™ on November 2, 2018. The European Commission has also approved DZUVEO (proprietary name in the U.S. as DSUVIA™) for the management of acute moderate to severe pain in adults in medically monitored settings. AcelRx is using AmerisourceBergan Corporation as their DOD prime vendor. The Defense Health Agency Clinical Advisory Committee approved the addition of DSUVIA™ to the Joint Deployment Formulary on July 7, 2020. Various U.S. Army medical assemblages (SKOs) were updated to include DSUVA™ on August 7, 2020. Current efforts by the Product Development Team revolve around ensuring that AcelRx post-marketing commitments for the drug are achieved and that the product is manufactured and available to the Warfighter.
The MS C/Full-Rate Production decision was approved by the Defense Health Agency Milestone Decision Authority on April 15, 2020.