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Finding Non-Opioid, Non-Addictive Solutions for Chronic Pain

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A recent report by the CDC reported that an estimated 20.4% of US adults (approximately 50 million people) suffer from chronic pain. Generally defined as any pain lasting for more than 12 weeks, chronic pain contributes to around $560 billion each year in direct medical costs, lost productivity, and disability programs. As a result of the heavy population burden, pain is considered a significant public health problem, and developing therapeutic options to combat this is necessary.


Physical pain can be divided into two main sectors: nociceptive and neuropathic pain. Nociceptive pain is the more common type and is caused by potentially harmful stimuli, either physical or mechanical, being detected by nociceptors around various parts of the body. In comparison, neuropathic pain is linked with damage to the body’s nervous system, generally caused by an infection or injury.

Treatment for nociceptive pain varies depending on the cause. Unlike neuropathic pain, nociceptive pain frequently responds well to treatment with opiates, such as codeine. Opiates have the ability to relieve pain through their action on the µ opioid receptor—the major analgesic opioid receptor expressed throughout the nervous system.

While evidence exists to support the use of opioids for the treatment of some acute and subacute pain and display their effectiveness, evidence to support their use to treat chronic pain is very limited, with surveys pointing out that just 23% of patients with chronic pain found opioids effective.

The long-term administration of an opioid for the treatment of chronic pain is mainly controversial with concerns related to effectiveness, safety, and largely, abuse liability. What began as over-prescription of opioids in the 1990s has led today to what is known as “The Opioid Crisis”, as opioid prescription rates more than tripled ultimately leading to close to 50,000 opioid overdose deaths in the US in 2017. Around 70% of all opioid overdose deaths involved a prescription opioid.


National Drug Overdose Deaths Involving Any Opioid
Number Among All Ages, by Gender, 1999–2017


Source: Center for Disease Control and Prevention, National Center for Health Statistics. Released December 2018


As the US fights this opioid epidemic, researchers and biotech companies have begun to aim their efforts at finding more effective and less harmful pain-relieving therapeutic options beyond opioids. Using Pharma Playbook, we were able to track what is going on in the ecosystem and who is leading the charge in this declared national public health emergency.


Increase in Research on Pain & Novel Approaches to Pain Relief
(June 2014–May 2019)


Source: Signals Pharma Playbook™ Insights


While most clinical trials investigating the effectiveness of various pain medications are in later stages of development, the early clinical trials, still in Phase 1, are aiming to focus on more novel targets beyond the opioid receptors.


Phases of Clinical Trials Focusing on New Pain Medications


Source: Signals Pharma Playbook™ Insights


Companies like Centrexion Therapeutics, CerSci Therapeutics, Levicept, and Astraea Therapeutics are solely focusing their pipeline on the development of non-opioid and non-addictive therapies to treat a broad array of chronic pain indications.

  • Centrexion recently completed a Phase 1 clinical trial testing their drug product, CNTX-6970, a CCR2 antagonist, which stops immune cells from releasing the potent cytokine MCP-1, thereby preventing MCP-1 from stimulating pain fibers to send pain signals. The results of the Phase 1 study showed the treatment was well-tolerated and demonstrated pharmacologic and pharmacodynamic activity (source). 

  • CerSci’s lead asset, CT-044, is a RSDAx (Reactive Species Decomposition Accelerant), which aims to degrade peroxynitrite and peroxide, two molecules formed as by-products of inflammation which aid in the transmission of pain signals. By destroying these molecules, CT-044 ultimately blocks pain signaling. CerSci recently received FDA approval to move forward with a Phase 1 clinical trial to assess the safety and tolerability of their novel non-opioid molecule (source).

  • Levicept is developing LEVI-04, which aims to modulate the neurotrophin pathway by binding excess neurotrophins present in chronic pain states and providing analgesia. Yet, at the same time, LEVI-04 maintains neurotrophin function required for cartilage and bone repair. LEVI-04 is currently in Phase 1 clinical trials (source). 

  • Astraea Therapeutics' AT-121 binds to the mu opioid receptor (MOR), similar to opioids such as morphine and oxycodone. However, AT-121 also binds to another opioid receptor called the nociceptin/orphanin FQ peptide (NOP) receptor. This interaction provides powerful pain relief while blocking many of the harmful side effects associated with opioids and may also have potential as a treatment for opioid addiction (source).

With the prevalence of chronic pain and opioid overdose deaths on the rise, the need for an effective, non-opioid and non-addictive solution for chronic pain is paramount. Young biotechnology companies are leading the way as they devote R&D resources to focus on novel targets to combat the opioid crisis. However, the field is yet to be saturated, and other companies are encouraged to investigate the underlying pain pathways which could bring about revolutionary therapeutics.


Insights powered by Signals Analytics’ Pharma Playbook

Pharma+Playbook (1)

Written by Shir Miodownik

Research Analyst at Signals Analytics

Shir completed her Masters in Genetics and Molecular Biology at Bar Ilan University, and is currently a medical student at Ben Gurion University.



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