Allosteric modulation company Addex Pharmaceuticals announced the presentation of phase-IIa data on ADX10059, an mGluR5 negative allosteric modulator, which shows efficacy in treating acute migraine attacks and provides evidence that inhibition of this glutamate receptor subtype could play a role in stopping migraine attacks before they start. Data were presented at the 61st Annual Meeting of the American Academy of Neurology (Seattle, USA).

"Medication is available to prevent migraine but these treatments are often secondary uses of the drug and come with potentially limiting side-effects," noted Dr Peter Goadsby of the UCSF Headache Center and investigator in the study. "New therapies specifically developed for migraine prevention are urgently needed especially for the substantial proportion of migraine sufferers who have frequent attacks and have significant disability in their daily lives. Targeting mGluR5 signalling with ADX10059 is an interesting approach that is showing significant promise in early clinical evaluation."

Preclinical experiments and small scale studies in migraineurs with drugs like ketamine, which acts on glutamate signalling through NMDA receptors (functionally related to mGluR5) and the NMDA antagonist memantine, suggest that mGluR5 could play a role in the 'migraine circuit', a positive feedback loop that generates the symptoms of a migraine attack. The initial step to test this hypothesis was Addex' proof of concept study in acute treatment of migraine attacks.

In the phase-IIa trial of 129 migraine patients presented at ANN, significantly more patients taking ADX10059 than those taking placebo (16.7 per cent vs 4.7 per cent, respectively p = 0.039) were pain-free two hours after dosing. ADX10059 administration yielded better pain improvement than placebo at all time points up to two hours after treatment of a migraine attack. In addition, there were trends to superiority for ADX10059 over placebo for migraine pain improvement (mild or no pain) at all time points up to two hours post-dosing.

"The clinical trial data for ADX10059, presented here at AAN, proved the concept that by terminating acute attacks in some patients, mGluR5 inhibition plays a role in migraine pathophysiology. Now we are looking forward to the data from our ongoing phase-IIb migraine prevention study in the first half of 2010," said Charlotte Keywood, chief medical officer.

In December 2008, Addex initiated a phase-IIb trial to study ADX10059 as a prophylactic agent in migraine. The 12-week trial will compare ADX10059 (25mg, 50mg or 100mg) versus placebo in migraine patients who suffer three or more attacks per month. Data from the migraine prevention trial are expected in the first half of 2010.

Addex Pharma discovers and develops allosteric modulators for human health.