Glutamate Receptor "mGluR5" Implicated in GERD

Data Published in GUT Shows Addex' ADX10059 Reduces GERD Symptoms in Patients

28-May-2009 - Switzerland

Addex Pharmaceuticals is pioneering a new approach to the treatment of gastroesophageal reflux disease (GERD), a common disorder affecting approximately 15 percent of people. GERD is the cause of commonly recognized unpleasant symptoms like heartburn, acid brash and reflux. By inhibiting metabotropic glutamate receptor 5 (mGluR5) signaling with ADX10059, a negative allosteric modulator (NAM) of mGluR5, Addex believes that the functioning of the lower esophageal sphincter can be normalized, thereby reducing exposure of the esophagus to acidic stomach contents and treating symptoms by addressing the cause of GERD.

Clinical data, published in the journal GUT and to be presented next week at the Digestive Disease Week conference, demonstrated that following administration of ADX10059 for a single day, patients reported fewer and shorter episodes of GERD symptoms compared to when they received placebo (2 versus 7 episodes, with a mean total duration of 5 minutes versus 14 minutes for placebo). This reduction in symptoms was associated with a statistically significantly reduction in duration of esophageal acid exposure, during the 24 hour pH monitoring period, compared to placebo. The researchers also found that night time reflux, which causes sleep disturbance and increased risk of esophageal damage, and reflux events following meals were also significantly reduced by ADX10059 therapy.

Data from a Phase I study of a modified release formulation of ADX10059, which supported the findings of the above study in GERD patients, also will be presented at DDW. This study in healthy volunteers showed that, compared to placebo, the new formulation of ADX10059 reduced the occurrence of reflux events on impedance pH monitoring, following intake of a refluxogenic breakfast. The modified release formulation also achieved the objective of improving the side effect profile seen previously with the immediate release formulation, and in reducing the dosing interval to twice daily from three times daily. Phase IIb trials with ADX10059 in GERD, both as a monotherapy and, separately, in combination with proton pump inhibitor (PPI) treatment are ongoing in the U.S. and EU.

"mGluR5 inhibition with ADX10059 represents a novel way of potentially treating GERD. These data published in GUT and to be presented at DDW represent some of our early clinical experience with ADX10059. Our Phase IIb studies are progressing well and we expect to report data on both the monotherapy and PPI combination studies late in 2009," said Charlotte Keywood, chief medical officer at Addex.

Original publication: "A proof of concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and symptoms in gastro-esophageal reflux disease"; GUT 2009.

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