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. Post-operative 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, post-operative 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

Physicians manage both acute and chronic pain through combination therapy, including the use of local anesthetics, analgesics, anti-inflammatory medications, neuropathic drugs, and/or opioids. Opioids are the cornerstone of pain management, but the need for non-narcotic pain alternatives and new options for multimodal pain management remains high. In 2014, there were more than 550 million pain medication prescriptions dispensed in the US, of which more than 250 million were opioids.5

Annual Rx in US5

Annual Rx in US

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 2000.6

Deaths Due to Opioid Overdose: US, 2000-20136

Deaths Due to Opioid Overdose: US, 2000-2013

Long-term use of opioids can lead to physical dependence or addiction, and it is estimated that between 28-38 million people worldwide currently use opioids as an illicit drug.6 These issues have made the development of novel pain interventions with lower abuse potential an area of urgent need.

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 post-operative 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 injected formulation may offer enhanced pain relief for patients relative to currently marketed interventions for post-operative pain, while at the same time reducing the dependence on opioid pain medications.

1. Centers for Disease Control and Prevention: National Hospital Discharge Survey. http://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. Symphony Health Solutions. http://symphonyhealth.com/. Accessed October 4, 2016.

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