Neuropathic pain is caused by damage to the peripheral nerves, as occurs in diabetic neuropathy. Neuropathic pain is difficult to treat, and many patients have pain that is refractory to existing treatments. Omnitram is a novel mixed-mechanism analgesic developed by Syntrix that consists of the (-) and (+) enantiomers of O-desmethyltramadol. The (+)-enantiomer is a potent -opioid receptor agonist, while the (-)- enantiomer is a norepinephrine reuptake inhibitor that synergizes with the (+)-enantiomer. Omnitram is inherently an opioid-sparing opioid-adjuvant combination therapy that is predicted to have low abuse potential. O-desmethyltramadol is the primary metabolite (M1) of tramadol. Omnitram provides the same net pharmacology as tramadol, but in contrast to tramadol, does not require metabolism by cytochrome P450 2D6 (CYP2D6) for its activity (i.e. it is metabolism-independent). Individuals who are CYP2D6 poor metabolizers (PMs) fail to obtain pain relief from tramadol. The real world incidence of CYP2D6 PM status in patients on polypharmacotherapy is as high as 1 in 3. Omnitram is therefore an opportunity to develop an improved tramadol that is effective in all patients irrespective of their CYP2D6 metabolic status. Omnitram successfully completed a Phase 1b randomized, double-blind, placebo-controlled trial that demonstrated Omnitram provided significant analgesia compared to placebo in an experimental pain model in healthy subjects. This Fast-Track application aims to further the success of the Omnitram program by demonstrating analgesic efficacy in patients suffering from neuropathic pain due to diabetic neuropathy. A Cochrane systematic review concluded that tramadol is an effective treatment for neuropathic pain with efficacy similar to that reported for antidepressants and anticonvulsants. Omnitram provides the same net pharmacology as tramadol and is therefore predicted to be efficacious in treating neuropathic pain.
Neuropathic pain is difficult to treat, and many patients have pain that is refractory to existing treatments. The most commonly studied neuropathic pain subtypes include diabetic neuropathic pain (DNP), postherpetic neuralgia (PHN) and HIV-related neuropathic pain. Collectively, these three conditions were estimated to affect over 6 million people across the seven major pharmaceutical markets (the United States, Japan, France, Germany, Italy, Spain and the United Kingdom) in 2010. However, the total affected population is considerably larger owing to the number of additional neuropathic pain conditions, such as neuropathic lower back pain, cancer-related neuropathic pain, complex regional pain syndrome and postoperative neuropathic pain. Due to the staggering human and economic costs, neuropathic pain represents a significant burden to public health. This Fast-Track proposal would advance a novel mixed-mechanism analgesic (Omnitram) towards clinical evaluation in patients suffering from neuropathic pain.