About Pain Management

Pain is one of the most widespread conditions in the world affecting patient health and quality-of-life. Pain can be acute or chronic in nature. Postoperative pain, one of the most serious forms of acute pain, remains an area of particularly high unmet medical need. Each year, there are more than 69 million surgeries performed in the US1 and 234 million surgeries performed globally.2 According to a 2014 survey, postoperative pain remains the most prominent surgery-related concern among patients.3 Following surgery, 65% of patients will experience moderate-to-severe pain, with little improvement in these rates over the last two decades despite advances in surgical techniques and pain management. Following discharge, 46% of patients still suffer from moderate-to-severe pain, and pain remains the leading cause of unanticipated hospital readmission following surgery.4

The opioid epidemic in the United States has reached a state of crisis. From 2000 to 2015, deaths from opioid overdoses more than tripled, lowering national life expectancy rates more than Alzheimer’s, liver disease, and car accidents combined.5

Reducing exposure to opioids in the postoperative setting is a key way to help curb the opioid epidemic in the United States. Each year, more than 50 million surgical procedures happen and 80% of patients undergoing a surgical procedure are prescribed opioids for pain management.6,7 As many as 6.5% of patients (about 2.6 million people) that take opioids to manage pain after surgery may become persistent opioid users.6 Of these 2.6 million persistent opioid users, approximately 440,000 will become addicted to opioids.8 In addition, opioid discharge prescriptions filled by recovering surgical patients result in more than a billion unused pills.9,10 Studies have shown that 70% of all these opioid tablets go unused, 90% of these pills remain inside the home in unsecured locations and 32% of all opioid addicts report first opioid exposure through leftover pills.7,11,12

There is a major unmet medical need for innovative non-opioid postoperative pain alternatives as well as new options for multimodal pain management. By preventing unnecessary exposure to opioids after surgery, we can stop addiction before it begins.

While opioids can be highly effective, this class of drugs is associated with significant medical and public health concerns. Patients commonly experience sedation, dizziness, and significant gastrointestinal issues including nausea, vomiting, and constipation. High doses of opioids can even cause life-threatening respiratory toxicity and death. In fact, opioids are the most common drug class implicated in deaths due to drug overdose, with the number of deaths due to opioid overdoses having nearly quadrupled since 2000.13 More than $13 billion of the annual healthcare costs associated with addiction can be attributed to postoperative pain management.14

Pain is a multifactorial condition involving multiple pathways.  Acute pain in response to local tissue injury, such as surgery, is mediated through two basic systems: local pain receptors in the skin or organs and a local inflammatory response.  First, local pain receptors will fire in response to injury, and these signals will travel through the nervous system to the brain to trigger central pain receptors.  Second, in conjunction with the firing of these pain receptors, injured tissue will also cause local inflammation, which reduces the efficacy of local anesthetics like bupivacaine and heightens the severity and duration of acute pain.

To address both underlying mechanisms of acute pain, we are developing HTX-011, an investigational, long-acting formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the prevention of postoperative pain. Bupivacaine blocks the firing of local pain receptors at the surgical site, while meloxicam works in synergy to reduce local inflammation at the surgical site. We believe that combining both modalities in a long-acting, locally applied formulation may offer enhanced pain relief for patients relative to currently marketed interventions for postoperative pain, while at the same time reducing the dependence on opioid pain medications.

1. Centers for Disease Control and Prevention: National Hospital Discharge Surveyhttp://www.cdc.gov/nchs/nhds.htm. Accessed October 4, 2016.

2. Weiser T et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet. 2008;372(9633):139-144.

3. Gan T et al. Incidence, patient satisfaction and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014;30:149-160.

4. Coley K et al. Retrospective evaluation of unanticipated admissions and readmissions after same day surgery and associated costs. J Clin Anesth. 2002;14(5):349-353.

5. Dowell D et al. Contribution of opioid-involved poisoning to the change in life expectancy in the United States, 2000-2015. JAMA. 2017;318(11):1065-1067.

6. Brummett CM et al. New persistent opioid use after minor and major surgical procedures in US adults. JAMA Surg. 2017;152(6):e170504. doi: 10.1001/jamasurg.2017.0504.

7. Hill MV et al. Wide variation and excessive dosage of opioid prescriptions for common general surgical procedures. Ann Surg. 2017;265(4):709-714.

8. Banta-Green CJ et al. Opioid use behaviors, mental health and pain--development of a typology of chronic pain patients. Drug Alcohol Depend. 2009;104(1-2):34-42. 

9. CDC 2017: Centers for Disease Control and Prevention. Opioid Overdose: U.S. Prescribing Rates Map. Available at https://www.cdc.gov/drugoverdose/maps/rxrate-maps.html. Accessed March 8, 2018.

10. Levy B et al. Trends in opioid analgesic-prescribing rates by specialty, U.S., 2007-2012. Am J Prev Med. 2015;49(3):409-413.

11. Bates C et al. Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol. 2011;185(2):551-555.

12. Canfield MC et al. Prescription opioid use among patients seeking treatment for opioid dependence. J Addict Med. 2010;4(2):108-113.

13. United Nations Office on Drugs and Crime: World Drug Report. http://www.unodc.org. Accessed October 4, 2016.

14. Council of Economic Advisers Report: The underestimated cost of the opioid crisis. https://www.whitehouse.gov/briefings-statements/cea-report-underestimated-cost-opioid-crisis/. Published November 20, 2017. Accessed May 7, 2018.