Addex reports positive results in Phase IIa clinical trial with ADX10059 in Migraine
Geneva, Switzerland 20 April 2007 – Addex Pharmaceuticals announced today the successful completion of a Phase IIa proof of concept trial with its lead compound ADX10059 in patients with migraine. The study achieved its primary objective, the absence of pain at 2 hours after dosing, with statistical significance, and also showed trends towards improvement in pain-free status and improvement of migraine pain at other time points. ADX10059 has already recently demonstrated a potential therapeutic benefit in a Phase IIa study in gastro-esophageal reflux disease (GERD), and is currently completing a Phase IIa study in anxiety.
ADX10059 is a potent, selective, negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5 NAM). Various pre-clinical pharmacology experiments have shown that glutamate is largely responsible for signal transmission in the neural circuit involved in migraine, and mGluR5 receptors are found at strategic points along the pathway. Inhibition of mGluR5 might therefore prevent the initiation of the migraine circuit, or interrupt it once established. For this initial exploratory study on the utility of an mGluR5 NAM in the management of migraine, an acute treatment paradigm was used.
The study was conducted in 129 migraine patients at opinion leader sites in the UK and Germany, according to the gold-standard design used for acute treatment of migraine. It comprised a multi-centre, double-blind, placebo-controlled comparison of a single dose of ADX10059 with placebo, to treat a single moderate or severe (IHS Grade 2 or 3) migraine headache, in an outpatient setting. Standard efficacy outcomes were used, with the primary efficacy variable being the proportion of patients pain-free (IHS Grade 0) 2 hours after dosing.
ADX10059 met the primary endpoint, showing a statistically significant higher number of patients pain-free 2 hours after dosing compared to placebo. At 2 hours post-dose, 16.1% of patients taking ADX10059 were pain-free compared to 4.5% taking placebo (p = 0.039). A benefit of ADX10059 on migraine pain could be seen from 1 hour after dosing, with the compound being numerically superior to placebo at 1.0 and 1.5 hours post-dose. The magnitude of active versus placebo response at 2 hours (3.6 fold for pain-free and 1.6-fold for mild/no pain) was similar to that seen in the acute treatment migraine trials for the triptans (see ref. 1 below). 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. For other secondary efficacy endpoints there were no statistically significant differences between the two dose groups.
"The study results show an important and novel principle in the treatment of migraine with the positive outcome using an mGluR5 receptor modulator. The data offer the real prospect of development of a completely new class of medicines that modulate the effects of glutamate and thus offer a neural - nerve-based - therapy for migraine sufferers," commented Professor Peter Goadsby, Institute of Neurology, Queen Square London, and Department of Neurology, University of San Francisco, California.
"These results are the first demonstration of the involvement of mGluR5 in the migraine process," said Dr Vincent Mutel, CEO of Addex. "We believe that ADX10059 could play a significant role in the long term management of this disease, and have given the green light to initiate a Phase IIb trial."
Migraine is a condition characterized by recurrent episodes of headache accompanied by a variety of other symptoms such as nausea, light and sound sensitivity, and fatigue. Attacks may be preceded by aura (usually visual phenomena such as flashing lights, zigzag lines and loss of visual fields) in about 40% of patients. An average migraine patient suffers 12 attacks a year, with an attack duration of between 4 and 72 hours. The prevalence of migraine is estimated at 12%, affecting approximately 30 million people in the United States. The disabling nature of migraine often results in a significant deterioration in quality of life for the sufferers and has a significant impact upon their work and family life. In the United States migraine is currently estimated to cost employers $13 billion annually in lost productivity. The total worldwide market for prescription migraine drugs was estimated at $2.4 billion in 2005, with the United States being the major market with sales of approximately $1.5 billion. The market is projected to increase to $2.7 billion by 2008. The mainstay of the prescription drug market for acute treatment of migraine in the last 10 years has been the triptan class of drugs, which are acute symptomatic treatments that have not been developed for use as migraine prevention agents. There is a significant unmet medical need for the latter, and an efficacious and well-tolerated medication with a neuronal rather than a vascular mechanism of action is currently considered by key opinion leaders to be the optimum drug profile for the prevention of migraine.
About Addex Pharmaceuticals
Addex Pharmaceuticals is an innovative company focused on the discovery and development of novel therapeutics that modulate the effect of natural activators on their specific targets, in particular G-Protein Coupled Receptors (GPCRs), in a non-competitive manner. The compounds are referred to as allosteric modulators and potentially offer advantages over conventional competitive agonist and antagonist compounds. This modulator principle is applicable to any GPCR, opening up a very wide variety of therapeutic opportunities. Addex is focusing its research and development on major indications with substantial unmet medical needs and significant commercial opportunities.
Addex has a portfolio of proprietary compounds in discovery and development for GERD, migraine, anxiety, smoking cessation, depression, pain, cognitive impairment, schizophrenia and Parkinson's disease. Addex's competence in drug development and its expertise in allosteric modulation were recognised in a collaboration established in 2004 with Ortho-McNeil Pharmaceutical, Inc., a member of the Johnson & Johnson Group.
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