Addex Starts a Second Phase IIb Trial of ADX10059 in GERD
Geneva, Switzerland, 17 December 2008 – Addex Pharmaceuticals (SWX:ADXN), the allosteric modulation company, announced the start of a Phase IIb trial of ADX10059 monotherapy in patients with gastroesophageal reflux disease (GERD), the cause of heartburn and other symptoms. ADX10059 is a first-in-class reflux inhibitor that works by reducing activation of the metabotropic glutamate receptor 5 (mGluR5) through negative allosteric modulation (NAM). This approach may lead to a new class of drugs that addresses the causes of GERD rather than just the symptoms.
Chief Medical Officer Charlotte Keywood said: “We have already observed significant efficacy with ADX10059 in two clinical studies in GERD. This Phase IIb study will allow us to assess the potential of ADX10059 as a stand alone treatment for clinical symptom control in GERD sufferers as well as further understand how ADX10059 works on lower esophageal sphincter function.”
Study ADX10059-204 is a double-blind, placebo-controlled, multi-center European Phase IIb trial in about 90 GERD patients known to respond well to proton pump inhibitors (PPIs). There will be a two week baseline symptom evaluation period followed by two weeks of administration of ADX10059 120 mg twice daily. ADX10059 will be used as a monotherapy so patients in the study will not use PPIs or other acid suppressant therapy during the baseline and study treatment periods. The primary endpoint is patient reported symptom control compared to baseline. Objective measures of the effects of ADX10059 on lower esophageal sphincter (LES) function and acid reflux events will be made in a subset of patients using esophageal manometry and pH impedance monitoring.
Addex announced on December 2 the start of Study 205, a double-blind, placebo-controlled, multi-center U.S. and European Phase IIb trial in about 280 GERD patients who are partial responders to PPIs. In Study 205 ADX10059 is being used as an add-on therapy to the patients’ existing PPI treatment. There will be a baseline symptom evaluation period followed by four weeks of administration of twice-daily ADX10059 (50mg, 100mg or 150mg). The primary endpoint is patient reported symptom control compared to baseline. Data for both studies are expected to be reported in late 2009.
Gastroesophageal reflux disease (GERD) is a chronic condition caused by stomach contents flowing back into the esophagus on a regular basis. The underlying cause of this is an abnormally functioning lower esophageal sphincter (LES) muscle that allows stomach contents to pass too easily back into the esophagus. GERD leads to painful symptoms like heartburn and can also damage the lining of the esophagus. It is a common disorder with prevalence at about 15% in the United States and between 10% and 25% in Marketed GERD products work by reducing the acidity of the stomach contents but do nothing to reduce reflux events, so that in many patients symptoms of GERD persist.
In GERD, inhibition of mGluR5 aims to restore normal function of the LES muscle thereby preventing reflux and addressing the cause of the disease. Indeed, ADX10059 has been shown by Addex to reduce reflux and reduce esophageal acid exposure in two separate clinical trials. Research has shown that mGluR5 inhibition improves LES function in animals. Reflux inhibitors have been recognized as potentially being the next generation GERD therapy because they address the cause of the disease and are complementary to marketed acid suppression therapies. Inhibition of mGluR5 has therapeutic potential in multiple other indications because, as with other glutamate receptors, mGluR5 is involved in a variety of functions in the central and peripheral nervous systems*. In addition to GERD, mGluR5 inhibitors have achieved clinical proof of concept in separate studies in patients with migraine headache, Parkinson’s disease levodopa induced dyskinesia (PD-LID) and generalized anxiety disorder (GAD). Inhibition of mGluR5 also has potential in Fragile X syndrome.
*mGluR5 antagonists: Discovery, characterization and drug development, Current Opinion in Drug Discovery & Development 2008 11(5):655-665
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 patients better results than classical drugs. Our lead allosteric modulator product, ADX10059, has achieved clinical proof of concept for the treatment of GERD and migraine, both important diseases for which existing products with limited efficacy have established multi-billion dollar markets despite sub-optimal benefits to patients.
Our products and technology already have proven their value through our relationships with four of the best pharmaceutical companies in the world. Specifically, in two separate agreements with Merck & Co., Inc., signed in December 2007 and January 2008, we are developing allosteric modulators as drugs to treat Parkinson's disease and schizophrenia, respectively. A third agreement, with Johnson & Johnson, is focused on development of allosteric modulators to treat anxiety and schizophrenia. Separately, the investment funds of Roche and GlaxoSmithKline have extended their validation of our technology, products and management by making significant 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.