Neuropathic pain – EMA401

Pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system is notoriously difficult to treat

Neuropathic pain is notoriously difficult to treat. Defined as pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system, it can have many different causes, such as diabetes, cancer and chemotherapy used to treat it, viruses such as herpes, which leads to postherpetic neuralgia, and nerve damage. Drug treatments are available, including the anticonvulsant pregabalin and the antidepressant duloxetine, but there is little or no effect in many patients, and side-effects can be dose limiting.

An alternative treatment is being developed by Australian biotech company Spinifex. EMA401 is an angiotensin II type 2 receptor antagonist. Angiotensin II type 1 receptor antagonists are familiar as treatments for hypertension, but blocking the AT2 receptor has no impact on blood pressure. Rather, it appears to relieve symptoms of pain in animal models of both neuro-pathic and inflammatory pain.

EMA401

EMA401 is therefore being developed as a potential treatment for patients with neuropathic pain, having been shown to inhibit capsaicin responses and neurite outgrowth in the lab in both rat and human sensory neurons,1 and also have efficacy in a rat pain model.2

Positive results were achieved in a first Phase II trial, in patients with postherpetic neuralgia. In the placebo-controlled, double blind, randomised trial, 183 patients who had been suffering from the condition for at least six months were given oral twice daily 100mg doses of EMA401 or placebo for 28 days.3 Those given the drug reported significantly lower levels of pain in the final week of treatment compared with baseline than those in the placebo group. In addition, a significantly greater proportion of those given EMA401 reported a reduction of more than 30% in their mean pain intensity score compared with baseline.

A sub-group of patients continued to take a single existing medicine during the study, and those given EMA401 also achieved significantly better pain relief than the placebo group, indicating that it may be useful in patients who fail to achieve optimal pain relief on current treatments. It caused no serious adverse events, and about a third of subjects in each group reported treatment-emergent adverse events.

References

1. U. Anand et al. Eur. J. Pain 2013, 17, 1012

2. M.T. Smith et al. Pain Med. 2013, 14, 692

3. A.S.C Rice et al. Lancet, 2014, epub ahead of print doi: 10.1016/S0140-6736(13)62337-5

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