A New Target for Neuropathic Pain?

Authors: Rice ASC et al., Lancet 2014 May 10; 383:1637

This is for our readers that treat pain patients.

A phase 2 trial demonstrates the potential of angiotensin II type 2 antagonists, a new treatment target, to relieve the chronic neuropathic pain of postherpetic neuralgia.

Because existing treatments for postherpetic neuralgia are often insufficient or ineffective, researchers have been investigating EMA401, an oral angiotensin II type 2 (AT2R) antagonist. For the current multicenter, placebo-controlled, double-blind, randomized, phase 2, manufacturer-sponsored clinical trial, 183 participants with established postherpetic neuralgia received either EMA401 (100 mg twice daily) or placebo for 28 days. Trial sites were in eastern Europe, Ukraine, and South Africa. The primary outcome was the change in mean pain intensity, according to a 0–10 scale, as recorded in weekly patient-completed diaries.

During the last week of treatment, patients given EMA401 had significantly less pain compared with baseline than did those given placebo (mean reductions in pain scores, −2·29 vs. −1·60; difference of least square means, −0·69, a significant difference). No serious adverse events attributable to EMA401 were reported.

Comment

In this well-designed and well-analyzed phase 2 clinical trial, the AT2R antagonist EMA401 has analgesic efficacy in postherpetic neuralgia. Although a net reduction of less than 1 point on an 11-point scale might seem small, it is in fact comparable to the best available orally administered treatments. No biomarkers were included, as none is validated for chronic pain. The treatment period was short; subsequent studies will need to demonstrate that the compound maintains efficacy relative to placebo for 12 weeks. No other trials of this medication category have been reported. The adverse event profile was encouraging, especially the lack of sedation or other effects that are drawbacks to existing approved therapies for pain. Despite the small market potential of PHN, analysis of numerous clinical trials has shown that PHN is a better model than painful diabetic neuropathy for evaluating new neuropathic pain therapies. The biggest obstacle to eventual approval of EMA401 will be the requirement to replicate the results in larger studies of much longer duration and in a larger range of study sites.