Neuropathic Pain

Neuropathic Pain

Neuropathic pain (NP) affects approximately 33 million people in the United States (excluding individuals with back pain) according to an article published in the Journal of Pain Research in 2017.1 NP is a complex, chronic pain state characterized by a steady burning "pins and needles" or "electric shock" sensation that results in abnormal neuronal function after nerve damage. The American Chronic Pain Association has identified various causes of NP, including tissue injury, nerve damage or disease, diabetes, infection, toxins, certain types of drugs, such as antivirals and chemotherapeutic agents, certain cancers, and even chronic alcohol intake. Current treatments for NP include antidepressants, anticonvulsants (such as gabapentin and pregabalin), and opioids, among others. However, current medications may offer inadequate efficacy, have limiting side effects, and may be associated with abuse.

Neuropathic Pain

VistaGen’s Innovation:

The effects of AV-101 as a potential new treatment for NP were assessed in published peer-reviewed preclinical studies involving four well-established models of pain. In these studies, AV-101 was observed to have robust, dose-dependent anti-nociceptive effects, as measured by dose-dependent reversal of NP in the Chung (nerve ligation), formalin and carrageenan thermal models in rats, and was well-tolerated. The publication, titled: “Characterization of the effects of L-4-chlorokynurenine on nociception in rodents,” by lead author, Tony L. Yaksh, Ph.D., Professor in Anesthesiology at the University of California, San Diego, was published in The Journal of Pain in April 2017.2 In recent studies in this preclinical model, AV-101 also had positive results using pregabalin (Lyrica®3) as an active control. AV-101 demonstrated robust analgesic effects, similar to Lyrica, but fewer side effects as measured in the rotarod assay. Neurontin4 and Lyrica have been associated with sedation and mild cognitive impairment in third party literature and are often prescribed for treatment of NP. Other commonly prescribed medications for NP include drugs targeting opioid receptors in the brain. Unfortunately, misuse of such drugs can lead to a significantly increased risk of addiction, and, we believe, their therapeutic utility for neuropathic pain is unclear.

Development Status:

Based on successful preclinical studies involving AV-101, gabapentin and pregabalin, as well as AV-101’s exceptional safety profile in all preclinical and clinical studies to date, upon successful Phase 1b development of AV-101 in combination with probenecid, we may explore Phase 2a clinical development of AV-101, together with probenecid, as a potential new generation, non-opioid treatment to reduce debilitating NP, avoid sedative side effects and cognitive impairment that have been observed in third party literature to be associated with other NP treatments, and reduce the risk of addiction associated with pain medications targeting opioid receptors.

The FDA has granted Fast Track designation for the development of AV-101 as a potential new, non-opioid treatment of NP.