The prevalence of pain in the US reached 178 million adults in 20141 with 50 million suffering from chronic pain, and 20 million with high impact pain i.e., chronic pain that frequently limits life or work activities5 . The economic costs of pain in the US from health care requirements and lower worker productivity range from $560 billion to $635 billion6 , with the human costs of unrelieved pain including physiological changes on CV, GI, respiratory, musculoskeletal, genitounrinary, and immune systems, as well as psychological and cognitive effects7.
Acute pain often starts suddenly, typically serving as an alert to disease or injury, with therapy being aimed at treating the underlying cause of the pain. Surgery is a common cause of acute pain and its control is an essential component of patient care. Unrelieved pain can have adverse consequences on the immune, cardiovascular, gastrointestinal, and renal systems, mood and ambulation8.
Chronic pain is pain that continues beyond the normal time of healing and includes ailments such as severe headache, back pain, cancer pain and arthritic pain. It is generally defined as lasting more than 12 weeks, is a common cause of long-term disability in the U.S, and can adversely affect patients’ sleep, cognitive processes, mood, cardiovascular health, sexual function and overall quality of life 9. Treatment often requires a multidisciplinary approach and more than one therapeutic modality.
Opioids have historically been a mainstay of treatment for patients with moderate-to-severe acute and chronic pain, despite the inherent risks and issues of life-threatening respiratory depression and opioid-induced side effects such as nausea, vomiting, constipation and somnolence, in addition to addiction.
Postoperative pain is the biggest concern for patients going into surgery10. Approximately 86% of surgical patients report postoperative pain and 75% report it to be extreme or moderate severity in the immediate postoperative period10. With over 100 million procedures performed each year in the US, postsurgical pain represents a significant healthcare burden. Analgesia in the surgical setting is important for patient comfort, recovery, reduction in hospital length of stay and hospital costs11.
Pain in the immediate postoperative period is typically treated with schedule II injectable opioids (79% of the total volume of injectable analgesics, mainly hydromorphone, morphine and fentanyl). It is also treated with IV non-opioids (21% of injectable analgesics, mainly ketorolac). Injectable ketorolac (brand name Toradol injection) makes up 17% of the overall injectable analgesic market, and is being used increasingly in the postoperative setting.
Unmet Need in Postoperative Pain
Neumentum’s products aim to address shortfalls in current pain management practices by offering patients and professionals safer and more effective pain treatment options. Neumentum’s lead product candidate, NTM-001 (Ketorolac PMB – Pre-mixed Bag), represents a highly efficacious, well-established NSAID aiming to provide stable pain relief by continuous infusion for up to 24 hours. NTM-001 may reduce analgesic gaps for patients without opioids and may eliminate the need for multiple doses, ensuring patients cannot exceed the dose ceiling. Additionally, NTM-001 is an alcohol-free formulation, avoiding pain for patients upon injection. Neumentum’s product candidates may reduce institutional liability and administrative burdens, supplying convenient, safe, effective and economical medicines for patients and caregivers. Learn more about Neumentum’s products here.
Unmet Need in Acute Pain in the Community Setting
There have been minimal advancements in the field of acute pain management and many of today’s compounds are considered first generation, were discovered decades ago and come with inherent risks. (e.g, Vicodin (hydrocodone/APAP – first approved 1943) or Percocet (oxycodone/APAP) first approved 1976). Nearly seven billion days of oral acute pain therapy are sold each year in the US, excluding neuropathic pain treatments. Over half (52%) of these are for opioids including 42% for immediate release formulations alone (e.g., brands such as Dilaudid (hydromorphone), Roxicodone (oxycodone) or in combination with acetaminophen (e.g., brands such as Percocet (oxycodone/APAP) or Vicodin (hydrocodone/APAP)) and 10% for other weaker opioids such as Ultram (tramadol). Several NSAIDs, including Cox-2 inhibitors, make up most of the remaining volume.
Today we have a greater understanding of the physiology of pain and mechanisms involved when someone is experiencing pain in their body. One such underexplored mechanism is that of adenosine A3 receptor modulation. Adenosine A3 receptor modulators (ARMs) are known to be involved with pain and inflammatory responses, and are a novel target in the search for new analgesics. More research into ARMs, and other pain pathways is needed to find safe and efficacious alternatives to opioids for patients with moderate to moderately severe acute pain.
Neumentum aims to address shortfalls of current pain management treatments by developing and commercializing effective and safe, non-opioid analgesic options without the risks of abuse, misuse and diversion seen with opioid analgesics, nor the opioid related risk of life-threatening respiratory depression. Neumentum has two late-stage product candidates that, if successfully developed through further clinical trials and ultimately approved by the FDA, will provide new options for patients and professionals:
- NTM-001 (NTM-001 (Ketorolac PMB–Pre-Mixed Bag) is a novel, alcohol-free formulation of the powerful NSAID ketorolac in a pre-mixed bag (PMB) designed for 24 hours of continuous infusion. It is being evaluated for the management of moderately-severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. This novel formulation is designed to address the limitations of existing forms of ketorolac. It allows for administration of the highly efficacious, well-established NSAID by continuous infusion for 24 hours, reducing or eliminating gaps in analgesia and the need for opioids which may occur at the end of the traditional bolus ketorolac dose. NTM-001 is an alcohol-free formulation that is expected to eliminate the pain that patients experience upon repeated dosing with traditional alcohol-containing bolus doses of ketorolac. If approved, NTM-001 will provide patients, professionals and institutions with a powerful, non-opioid, injectable analgesic in a convenient ready-to-hang pre-mixed bag, offering around-the-clock analgesia without the side-effects, risks, and liabilities of opioids or the disadvantages of bolus ketorolac.
- NTM-006 is an oral, non-opioid and non-NSAID product under investigation to treat moderate to moderately-severe acute pain. It is in Phase 2 development with positive data from a Phase 2A dental pain study. NTM-006 has a novel mechanism of action, unlike that of opioids or NSAIDs – it is thought to interact with Adenosine-3 (A3) type receptors to modulate the activity of adenosine, a natural neurotransmitter whose level changes during periods of pain and stress. If successfully developed, NTM-006 is expected to offer effective pain relief for moderate to moderately severe acute pain in the hospital and community settings, without the serious risks associated with opioids or NSAIDs, as outlined in boxed warnings for these classes of analgesics.
Disclaimer: These are investigational new drug candidates and are not approved for any indication in any markets.
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