Addex Presents ADX10059 GERD Data at Conference
Paris, France, 29 October 2007 – Allosteric modulation company Addex Pharmaceuticals (SWX:ADXN, Geneva, Switzerland) presented new data from its Phase IIa trial of ADX10059 to treat gastroesophageal reflux disease (GERD) today at the United European Gastroenterology Week (www.uegw.org) conference in Paris, France. GERD is a common disorder, affecting about 15% of the population. New data released today for the first time show that ADX10059 controlled stomach acid reflux during the critical period following meals, when GERD can be most troublesome. Top-line data, first released in April, showed that the product controlled acid reflux over a 24 hour period.
“Despite the benefits of the leading prescription therapies for GERD, stomach acid reflux occurring after meals and at night remains a significant area of unmet need for GERD sufferers. The data from this early study with ADX10059 are encouraging as the compound appears to have meaningful effects at these times,” said Charlotte Keywood, chief medical officer at Addex. “Some studies indicate that about 50% of GERD patients are not adequately controlled by marketed therapies.”
The single-blind, placebo-controlled, two-day study was performed in 24 male and female GERD patients. The objectives were to evaluate the effect of ADX10059 on physiological measures of reflux and on the occurrence of patient-recorded clinical symptoms of GERD. On Day 1 patients received placebo, while on Day 2 they received ADX10059 half an hour before each of three meals. Meals were standardized and included high fat and acidic foods to provoke reflux episodes. The patients were unaware of the treatment sequence. Real time 24-hour pH recording was achieved using a pH sensor placed in the lower esophagus. The pH is a measure of acidity; decreasing pH indicates increasing acidity. Day 1 measurements were compared with Day 2 for each patient. The effect of two different doses, 50mg or 250mg of ADX10059, was tested, with twelve patient in the high dose group and twelve in the low dose group.
Newly released data show that, during the postprandial period (i.e. the period following meals), there was a reduction in the number of episodes and duration of episodes where the pH dropped (i.e. acidity increased) by more than one pH unit. This measurement suggests ADX10059 controls pH even when GERD patients eat a meal designed to induce reflux.
These data were presented at the UEGW meeting today during a session entitled, “GERD Treatment: Testing the Old and Introducing the New.”
The table below shows the mean number and duration of episodes where the pH drop was greater than or equal to 1 in the postprandial periods for the 11 patients in the high dose group.
|Postprandial Period||Treatment||Number of Episodes||p-value||Total Duration (mins)||p-value|
+ 4 hours
|Lunch + 4 hours||Placebo||6.1||ns||15.2||0.0371|
|Dinner + 4 hours||Placebo||7.1||ns||13.5||0.0146|
ns = not significant
Addex announced earlier this year that ADX10059 met the primary endpoint of 24-hour esophageal pH control compared to placebo. The trial also met a number of other secondary endpoints, including reducing the duration of acid exposure at night, a period when it can be particularly difficult to control GERD symptoms. Importantly, on average, patients reported less than one third the number of symptomatic GERD episodes (e.g. heartburn, acid brash or burping) when they received ADX10059. Furthermore, on average, when the episodes occurred, they lasted less than half as long when the patients received ADX10059.
The table below shows additional data from the trial for the 11 patients in the high dose group.
|Efficacy Variable||ADX10059 250mg t.i.d||Placebo t.i.d.||p-value|
|% time pH<4 in 24h (primary endpoint)||3.5||7.2||0.014|
|% time pH<4 nocturnal||3.7||9.7||0.0028|
|Median pH 24h||6.6||6.4||0.0015|
|Reflux pH<4 in 24h (n)||20.5||32.7||ns|
|Total duration reflux pH<4 24h (min)||40||86||0.0132|
|Reflux pH<4 nocturnal (n)||6.4||13.6||ns|
|Total duration reflux pH<4 nocturnal (min)||16.2||48.6||0.0021|
|No. episodes pH drop ≥1 24h||27.8||38.6||0.054|
|Longest duration pH drop ≥1 (min)||24.0||33.4||ns|
|Number of symptomatic episodes||1.9||7.0||0.031|
|Duration symptomatic episodes (min)||5.2||13.9||0.031|
ns = not significant
Although there were trends towards efficacy in some of the 12 patients receiving the low, 50mg dose of ADX10059, the average differences compared to placebo did not reach statistical significance. One patient in the 250mg group was not included in the efficacy evaluation because the patient did not complete pH monitoring because the probe was displaced. ADX10059 was generally well tolerated during the trial.
ADX10059, an experimental GERD therapy, works differently than marketed products for GERD. Most available drugs work by reducing acid production in the stomach and therefore reduce the side effects caused by GERD. In contrast, ADX10059 appears to work by reducing the flow of the stomach contents into the esophagus, thereby addressing the underlying cause of GERD. Addex believes ADX10059 improves the functioning of the lower esophagus such that the exposure of the esophagus to noxious stomach contents is reduced.
ADX10059 is an orally available small molecule compound that works as a negative allosteric modulator (an inhibitor) of the metabotropic glutamate receptor 5 (mGluR5). This receptor is believed to be important for the control of the lower esophageal sphincter. In animal models of GERD, blockade of mGluR5 has been shown to reduce the inappropriate openings of the lower esophageal sphincter and improve its muscle tone, normalizing its efficiency.
Gastroesophageal reflux disease (GERD) is a common disorder, affecting about 15% of the world’s population. In the vast majority of cases, GERD is not caused by excess acid production in the stomach but rather flow of stomach contents into the esophagus due to abnormal functioning of the lower esophageal sphincter. GERD can cause symptoms including heartburn, acid brash and belching. In some chronic cases, GERD can lead to a condition called Barrett’s esophagus, which can progress to cancer. Studies indicate that 50% of GERD patients are not adequately controlled by marketed therapies.
Addex Pharmaceuticals discovers and develops allosteric modulators, an emerging class of small molecule therapeutic agents. Allosteric modulation may offer more sophisticated ways to normalize biological signaling compared to classical “orthosteric” agonist or antagonist drugs. “Allosteric”, literally translated from its Greek roots, means: “other site”. Thus, allosteric modulators bind receptors at sites that are distinct from the binding sites of classical small molecule “orthosteric” agonist and antagonist drugs.
The most advanced drug candidate, ADX10059, a negative allosteric modulator (NAM) of metabotropic glutamate receptor 5 (mGluR5), recently demonstrated clinically and statistically significant efficacy in separate Phase IIa clinical trials in gastroesophageal reflux disease (GERD) patients and migraine headache patients. Data from another Phase IIa clinical trial of ADX10059 in acute anxiety are due around the end of 2007.
The Addex discovery capability has been validated through a collaboration with Ortho-McNeil, a Johnson & Johnson company. The deal is limited to discovery and development of allosteric modulators of metabotropic glutamate receptor 2 (mGluR2).
In May 2007, Addex completed an initial public offering on the SWX Swiss Exchange, raising CHF137 million ($111 million / €83 million). The IPO was the largest biotech IPO in Europe in three years.
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The foregoing release contains 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, and involve known and unknown risks, uncertainties and other factors that may cause actual results with ADX10059 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that ADX10059 will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that ADX10059 will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding ADX10059 could be affected by, among other things, 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 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.