Spinifex Pharmaceuticals, an Australian biotechnology company developing new drug candidates for the treatment and management of pain, has announced positive phase 2 clinical trial results from its lead product, EMA401, in postherpetic neuralgia (PHN), a painful condition that develops in some patients following herpes zoster (shingles) and where existing therapy does not relieve pain in all individuals.

The clinical trial met its primary endpoint, reduction in mean daily pain score versus placebo over the last week of 28 days of treatment. Results show a statistically significant  and clinically meaningful  reduction in mean pain intensity from baseline to  week 4 for subjects on active treatment when compared to placebo.  On an intent to treat basis, the mean pain intensity reduction from baseline after 4 weeks treatment was as follows: EMA401:  -2.34; Placebo:  -1.64; p = 0.006.

A significantly greater proportion of patients on active treatment reported a  more than 30% reduction  in mean pain intensity score compared to baseline (i.e. responder rate) (EMA401: 56.5%; Placebo: 34.1%; p = 0.003), meeting a key secondary endpoint.

EMA401 was generally safe and well tolerated with no serious treatment related adverse events reported.

The double-blind, placebo-controlled randomised trial was  recruited  at  29 centres in  six countries and enrolled  183 patients.  More details on the trial design and results can be found in the appendix.

Dr Milton Raff (Christiaan Barnard Memorial Hospital, Cape Town, South Africa), Principal Investigator for the Study, said: “These headline results are very promising with a clear reduction in pain versus placebo and a good safety and tolerability profile. EMA401 offers an entirely novel approach to  the treatment of PHN and could represent a valuable new option in an area where there is a clear need for new medicines. Current treatments for the condition are effective in some patients but a significant proportion either don’t respond to therapy and are left with debilitating symptoms or suffer significant side effects.”

Spinifex Pharmaceuticals CEO  Tom McCarthy said: “Today’s results are a major step for Spinifex and for the development of EMA401 as a treatment for neuropathic pain. It is tremendously gratifying for the Spinifex team to have taken a scientific discovery through to proof of clinical concept in what is a notoriously difficult  field and one where new treatments are clearly needed. We look forward to advancing EMA401 further in PHN and other neuropathic pain indications including cancer chemotherapy induced neuropathic pain and painful diabetic neuropathy. Ultimately we hope EMA401 becomes a  broad treatment for chronic pain in general.”

The market for neuropathic pain treatments is expected to continue to increase and is projected to reach US$6.2 billion by 2017. Despite this growth, current therapy needs to be improved as a significant proportion of neuropathic pain patients don’t respond to current therapy and these treatments have dose-limiting side effects. As a result, EMA401 is being developed as a potential first -in-class oral treatment for neuropathic pain and related symptoms without central nervous system side effects. In addition to PHN, Spinifex’s clinical program for EMA401 includes a phase 2 study in the treatment of  neuropathic  pain in cancer chemotherapy patients and this trial is currently recruiting.

EMA401 is  an angiotensin II type 2 (AT 2) receptor antagonist. The discovery that AT2   receptor antagonists offer an innovative approach to the treatment of neuropathic and inflammatory pain was originally made by Professor Maree Smith at The University of Queensland. Having acquired the technology, Spinifex has conducted a comprehensive pre-clinical and early clinical development programme on EMA401.  

In addition to positive Phase 2 results,  EMA401 has shown efficacy in a number of relevant  pre-clinical  models and good human safety and pharmacokinetics in phase 1 studies. Spinifex continues to conduct research into the role of the AT2 receptor in  nociceptive, inflammatory and neuropathic pain states and these fundamental studies support not only the EMA401  clinical programme but  also  Spinifex’s ongoing AT2   receptor antagonist drug discovery programme.