Introduction

Neuropathic pain (NeP) is a difficult-to-treat form of chronic pain that results from nerve damage. Reported to afflict between 7-8% of the general population, NeP has a significant, negative impact on patients’ quality of life. In fact, >35% of patients with neuropathic pain develop depression or anxiety. At best, only 15-25% of patients achieve a 50% reduction of symptoms with current first-line therapies and side effects are common. The other 75-85% of patients often receive little to no benefit from therapy leaving them struggling to find an effective treatment regime. It is clear that patients need new, effective therapies with a reduced side-effect profile.

Patient Population

While there are many forms and origins of NeP, the three most commonly studied subtypes are diabetic neuropathic pain (DNP), postherpetic neuralgia (PHN), and HIV-related neuropathic pain. Together, these three subtypes afflicted over 6 million patients across the United States, Japan, and Western Europe in 2010. Due to the increasing incidences of both diabetes and herpes zoster, the population of patients with NeP comorbidities will continue to grow. Estimates predict the U.S. market for NeP drugs will reach ~$3.6 billion by 2020.

Standard of Care

Current first-line therapies include tricyclic antidepressants (e.g. amitriptyline), serotonin and norepinephrine reuptake inhibitors (e.g. duloxetine), and antiepileptics (e.g. gabapentin and pregabalin). Side effects are common with these treatments and include somnolence, dizziness, nausea, and adverse anticholinergic effects in the case of tricyclic antidepressants.  Often, doctors must customize treatment plans to find one that is both efficacious and tolerable.

Second-line therapies typically include opioids and topical drugs (e.g. lidocaine, capsaicin). Opioids are effective in acute management of NeP. However, a systematic review of randomized trials found the evidence of benefit over three months “was poor based on either weak positive evidence or indeterminate or negative evidence.” (Christo, P.J. et al. Pain Physician 2011). In addition to the significant abuse potential of opioids, they are also associated with increased bone fracture, hospitalization and mortality which limits their usefulness -especially for the elderly. Although topical therapies may be efficacious in some patients, the therapeutic gain is usually modest vs. placebo.

NCT-10001  shows effective relief of neuropathic pain in animal models at doses that do not cause observable side effects.