444  0 Kommentare Addex ADX10059 Monotherapy is Effective on GERD Symptoms in Phase IIb Clinical Trial

"Based on its marked efficacy in both reducing reflux and controlling
symptoms in this study, I would be pleased to see ADX10059 tested in
later stage trials as a monotherapy for GERD patients, " said
professor Frank Zerbib, head of gastroenterology at the University
Hospital of Bordeaux and a leading expert on GERD. "Furthermore, the
good tolerability seen with this modified-release formulation of
ADX10059 was also a crucial part of these results, since GERD is a
chronic disease where long-term therapy is needed in the majority of
patients."

Vincent Mutel, CEO of Addex said, "These data confirm our belief in
using this mechanism of action, mGluR5 inhibition, to treat GERD.
Furthermore, we believe that the market potential for a product with
the profile of ADX10059 is very significant. We look forward to
further development of this molecule in GERD."

Study ADX10059-204 was a double-blind, placebo-controlled,
multi-center European Phase IIb trial in 103 GERD patients known to
respond well to proton pump inhibitors (PPIs). There was a two-week
baseline symptom evaluation period followed by two weeks of
administration of ADX10059 120 mg twice daily. ADX10059 was used as a
monotherapy so patients in the study did not use PPIs or other acid
suppressant therapy during the baseline and study treatment periods.
The primary clinical endpoint was the patient reported number of GERD
symptom free days in week 2 of treatment compared to the last 7 days
of baseline. Objective measures of the effects of ADX10059 on
esophageal function and reflux events were made in a subset of 24
patients on the day before starting treatment and on the last day of
treatment using impedance pH monitoring and esophageal manometry.
Reflux events on impedance pH monitoring were the mechanistic primary
variables.

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ADX10059 significantly increased the mean number of GERD symptom free
days in week 2 of treatment. At baseline the mean number of symptom
free days was 0.46 in the ADX10059 group and 0.72 days in the placebo
group. During treatment week 2 this increased to 2.5 days in the
ADX10059 group and to 1.71 days in the placebo group (p = 0.0452)

In the subset of 24 patients who underwent mechanistic monitoring
ADX10059 also achieved statistical significance in two mechanistic
primary endpoints. ADX10059 significantly reduced total impedance
measured reflux events and also acidic reflux events over the 24 hour
monitoring period. In the ADX10059 treated group the mean number of
total reflux events decreased by 26% from 64.9 at baseline to 47.9 on
treatment compared to no change in the placebo group with a mean of
77.0 reflux episodes at baseline and 78.4 on treatment (p = 0.0342).
In the ADX10059 group the mean number of acidic reflux events in 24
hours decreased by 29% from 52.1 at baseline to 37.0 at end of
treatment compared to a small increase in the placebo group with 55.7
episodes at baseline, and 59.7 at end of treatment (p = 0.0032).

In addition to the primary efficacy endpoints, ADX10059 showed
statistical superiority over placebo for a variety of secondary
variables including an increase in heartburn free days, a reduction
in sleep disturbance, a reduction in the requirement for antacid
medication, an improvement in a GERD symptom patient reported outcome
questionnaire (p<0.05 for all measures). Finally patients also
expressed a significant preference for ADX10059 treatment compared to
placebo (p<0.05).

ADX10059 120 mg twice-daily given for two weeks was well tolerated
and the tolerability profile seen is compatible with use in the
treatment of GERD. Adverse events were reported more frequently for
ADX10059 than placebo but in both treatment groups the vast majority
was mild and none was described as severe. There were no significant
changes in safety monitoring parameters.

Addex also announced today that enrolment has been completed in the
second trial of ADX10059 in GERD patients. In the study ADX10059-205,
the product is being used as an add-on therapy in patients who are
partial responders to Proton Pump Inhibitors (PPIs), the standard
therapy for GERD. Results are expected in January 2010. A third
trial, where ADX10059 is being studied as a migraine prophylaxis in
patients with frequent migraines is progressing as expected and data
will be reported in the second quarter of 2010.

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 back into the esophagus too
easily. 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 EU. 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.

mGluR5 inhibition in GERD aims to restore normal function and improve
the tone 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 three separate
clinical trials(1,2). Research has shown that mGluR5 inhibition
improves LES function in animals. Reflux inhibitors are being
recognized as potentially the next generation of 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(3). In addition to GERD, mGluR5 inhibitors have
achieved clinical proof of concept in separate studies in patients
with migraine headache(4), Parkinson´s disease levodopa induced
dyskinesia (PD-LID) and generalized anxiety disorder (GAD).
Inhibition of mGluR5 also has potential in Fragile X syndrome,
neuropathic pain and depression.

(1) Keywood, C., et al., GUT online May 20, 2009 (free download:
http://bit.ly/2Rcu0k)
(2) Zerbib, F., et al., Digestive Disease Week (DDW) 2009 (free
download: http://bit.ly/HjehE)
(3) Gasparini, F. et al., Current Opinion in Drug Discovery &
Development 2008 11(5):655-665
(4) Goadsby, P. et al., American Academy of Neurology (AAN) 2009
(free download: http://bit.ly/13aBkw)

Webcast and conference call today at 4pm CET (10am ET). Visit the
Addex website for more information.

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.
Addex 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.

Chris Maggos
Head of IR & Communications
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos@addexpharma.com

Disclaimer
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
allosteric modulators of mGluR4, mGluR2, mGluR5 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 mGluR4,
mGluR2 or mGluR5 will be approved for sale in any market or by any
regulatory authority. Nor can there be any guarantee that allosteric
modulators of mGluR4, mGluR2, mGluR5 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 mGluR4, mGluR2, mGluR5 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 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.

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