Spinifex Pharmaceuticals’ EMA401 Phase 2 Results Published in The Lancet

Spinifex Pharmaceuticals has announced that The Lancet has published the results of its Phase 2 clinical trial of its lead candidate, EMA401, in postherpetic neuralgia (PHN). EMA401 is a novel angiotensin II type 2 (AT2) receptor antagonist under development as a potential first-in-class oral treatment for chronic pain without CNS side effects. PHN is a painful condition that develops in some patients following herpes zoster (shingles) and where existing therapy does not relieve pain in all individuals.

The Phase 2 trial met its primary endpoint by showing that patients randomized to EMA401 achieved a greater reduction in pain from baseline to the last week of 28 days of treatment than patients randomized to placebo.

Analyzing all patients randomized (intent to treat population), the mean pain intensity reduction from baseline after 4 weeks treatment was as follows: EMA401: -2.29; Placebo: -1.60; p = 0.007.

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: 57.6%; Placebo: 35.2%; p = 0.0023), meeting a key secondary endpoint.

A subgroup of patients who had moderate or severe pain at study entry continued to take a single existing medicine for their PHN during the study (45% of patients in the EMA401 group and 40% of patients in the placebo group). In this subgroup, patients randomized to EMA401 achieved significantly greater pain reduction when compared to patients randomized to placebo.

In addition, pain relief was also observed in those patients that were not taking a single existing medicine for their PHN. These results indicate that EMA401 may have the potential to provide relief for patients with PHN who don’t achieve optimal pain relief with current treatments or who don’t wish to continue with these medicines due to their side effects.

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

In a commentary also published in the Lancet, Dr Nanna Finnerup, of the Danish Pain Research Center, Aarhus University, described this first clinical study to evaluate the efficacy of an AT2 receptor antagonist in neuropathic pain as encouraging adding: “Most importantly, their work identifies a possible new drug for the treatment of neuropathic pain with a novel mechanism of action, and thus offers hope for patients who have insufficient pain relief with presently available drugs.”

Andrew Rice, a Professor of Pain Research at Imperial College, Hon. Consultant in Pain Medicine at Chelsea and Westminster Hospital, and lead author of The Lancet paper said: “These results demonstrated EMA401 was able to significantly reduce pain in patients with postherpetic neuralgia and was well tolerated. This paper is the first publication of the clinical effects of any AT2 receptor antagonist and contributes to our understanding of the potentially important role of this new drug class in relieving chronic pain. These results are an exciting step in the development of a novel approach to the treatment of neuropathic pain and chronic pain more generally.”

Spinifex Pharmaceuticals’ CEO Tom McCarthy said: “There is a clear need for new treatments that bring patients pain relief with fewer CNS side effects. The publication of the Phase 2 data with EMA401 in such a prestigious publication is an endorsement of the quality of our scientific development capabilities. We are pleased The Lancet, in the associated commentary, recognizes the significant milestone we have achieved in translating basic science on a new pain pathway into clinical efficacy in patients. As stated in the commentary, in addition to PHN, we see broad potential for EMA401 to treat a range of chronic painful conditions such as pain due to osteoarthritis and diabetes. We look forward to delivering on the further development of EMA401.”