Addex’ ADX10059 has potential for Parkinson’s disease levodopa induced dyskinesia (PD-LID)
Geneva, Switzerland, 14 September 2009 – Allosteric modulation company Addex Pharmaceuticals (SIX:ADXN) reported today that its lead product, ADX10059, which is nearing completion of Phase IIb testing in gastroesophageal reflux disease (GERD) and migraine prevention, also has demonstrated significant potential in a non-human primate model of Parkinson’s disease levodopa induced dyskinesia (PD-LID).
ADX10059 is an allosteric inhibitor – a negative allosteric modulator (NAM) – of a glutamate receptor subtype called metabotropic glutamate receptor 5 (mGluR5). Phase IIb data are expected in the fourth quarter of 2009 for GERD (e.g. heartburn) and the first quarter of 2010 for migraine prevention.
In a recently completed study using the “MPTP” primate model, all doses of ADX10059 abolished levodopa induced dyskinesia in the first hour after levodopa administration. There was no adverse effect on Parkinsonian disability scoring. The 10mg/kg and 30mg/kg doses of ADX10059 significantly reduced dyskinesia (p<0.05) in the first two hours after levodopa dosing.
Addex also reported during its July R&D Day that in rats ADX10059 showed a dose dependent effect in reducing catalepsy induced by haloperidol, a rodent model of Parkinson’s disease.
PD-LID currently has no approved therapy. It is a complication caused by dopamine replacement (i.e. levodopa) therapy and characterized by a variety of hyperkinetic movements. Most PD patients develop LID after receiving levodopa for several years. Currently there are an estimated 1.2 million patients with PD-LID in the U.S. PD is a degenerative disease of the brain that often impairs motor skills, speech, and other functions. It is estimated that 60,000 new cases are diagnosed each year in the U.S., where more than 1.5 million people currently have PD. While the condition usually develops after the age of 65, 15% of those diagnosed are under 50. PD affects both men and women in almost equal numbers.
The rationale for using mGluR5 inhibition in PD is as follows. An imbalance of neurotransmitters resulting from the loss of dopamine producing cells leads to excess glutamatergic stimulation in the striatopallidal pathway. Inhibition of glutamate stimulation in this pathway is believed be important for anti-Parkinsonian effects. mGluR5 are found abundantly in the striatum and are implicated in the excess glutamate activity in Parkinson’s Disease. Blockade of mGluR5 has been shown to have anti-PD effects in a variety of animal models.
Data from Addex and other researchers show that mGluR5 inhibition has therapeutic potential in multiple indications. Addex has prioritized development in GERD and migraine; others are pursuing PD-LID, Fragile X syndrome and neuropathic pain.
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric modulators for human health. Allosteric modulators are a different kind of orally available small molecule therapeutic agent, which we believe will offer a competitive advantage over classical drugs. Our lead allosteric modulator product, ADX10059, has achieved clinical proof of concept and is in Phase IIb testing for the treatment of GERD and, separately, migraine headache. ADX10059 is a first-in-class mGluR5 inhibitor, a therapeutic strategy that also is being pursued in multiple indications by large pharma competitors.
Our products and technology already have proven their value through our relationships with four of the top 10 pharmaceutical companies in the world. Specifically, under an agreement with Ortho-McNeil-Janssen Inc., a Johnson & Johnson company, ADX71149, a positive allosteric modulator (PAM) of mGluR2, is undergoing Phase I clinical testing and has potential for treatment of schizophrenia and anxiety. Under two separate agreements with Merck & Co., Inc., we are developing PAMs of mGluR4 and mGluR5 as drugs to treat Parkinson's disease and schizophrenia, respectively. In addition, GlaxoSmithKline and Roche have made equity investments in Addex.
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The foregoing release may contain forward-looking statements that can be identified by terminology such as "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Pharmaceuticals Ltd, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Pharmaceuticals Ltd regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, and/or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such may in particular cause actual results with allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGluR2, mGluR4, mGluR5, mGluR7 or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Pharmaceuticals Ltd is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.