June 14, 2023
(press release)
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On May 9, National Fentanyl Awareness Day was observed in recognition of the US opioid crisis. Accordingly, the development of non-opioid painkillers is experiencing a surge in activity, and despite numerous novel targets receiving high levels of attention, cannabinoids have emerged as strong favorites to replace opioid-related medications. As a result, they hold the potential to be the future of pain medication and address the opioid epidemic, says GlobalData, a leading data and analytics company. The North American opioid epidemic highlights limitations in opioid use, such as the potential for drug abuse and overdose. According to the National Institute on Drug Abuse, drug-involved overdose claimed over 100,000 lives in 2021 alone. Nevertheless, opioid-based painkillers remain the primary approach for pain management, creating a need for effective drugs with alternative targets. According to GlobalData’s Drugs Database, there are currently 546 painkillers in active development, with 458 targeting opioid-receptor alternatives. A promising example includes Vertex Pharmaceuticals’ VX-548, a sodium channel subunit blocker. In 2022, the FDA awarded VX-548 breakthrough therapy and fast-track designations for post-operative pain, and the drug is forecast to reach sales of $416 million by 2029. Of the 458 drugs, drugs targeting cannabinoid receptors (CB) are currently the two most popular targets, with 35 drugs in development for CB2 and 32 targeting CB1, accounting for approximately 10% of pipeline drugs. These receptors interact with naturally occurring or synthetic cannabinoids to modulate a variety of physiological processes, including pain. CB1 is predominantly found in the central and peripheral nervous system, whereas CB2 is primarily located in immune cells. Jasper Morley, Drugs Intelligence Analyst at GlobalData, comments: “As drug targets, these receptors have demonstrated therapeutic value against different types of pain. However, along with other painkiller alternatives, doubts have been cast over their efficacy.” Six cannabinoids have recently completed or are undergoing Phase II trials. A leading CB2 agonist, olorinab, displayed encouraging results when managing abdominal pain in irritable bowel syndrome (IBS) patients, but failed to meet the primary efficacy endpoints. In 2022, Pfizer acquired the drug, with the promise of accelerating clinical development via new, differentiated, and best-in-class approaches, enhancing optimism for further drug development. Currently, Jazz Pharmaceuticals’ nabiximols is the only cannabinoid approved for pain, receiving approval in Israel in August 2010. However, 2017 saw the discontinuation of nabiximols from Phase III development in the US for cancer pain, due to a lack of efficacy. Unfortunately, issues with efficacy seem to be a recurring theme, with AstraZeneca discontinuing its non-opioid painkiller, AZD-1704, from Phase I development, for a similar reason. Morley concludes: “Although efficacy concerns hinder the use of cannabinoids as a solution to the crisis, intensified research contributes to a better understanding of this domain, enabling a greater efficacious potential of future marketed treatments. The large number of pipeline cannabinoid painkillers suggests the future of pain medication may lie within this area, instilling hope for a future reduction in opioid manufacturing and prescriptions, and a potential route out of the crisis.”
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