Addex Presents Data on ADX10059 at the Annual Meeting of the American
Academy of Neurology
English (PDF)
Data Suggests Glutamate Receptor "mGluR5" is Clinically Relevant for
Migraine
Geneva, Switzerland, April 29, 2009 - Allosteric modulation company
Addex Pharmaceuticals (SIX:ADXN) announced today the presentation of
Phase IIa data on ADX10059, an mGluR5 negative allosteric modulator,
which shows efficacy in treating acute migraine attacks and provides
evidence that inhibition of this glutamate receptor subtype could
play a role in stopping migraine attacks before they start. Data were
presented at the 61st Annual Meeting of the American Academy of
Neurology (Seattle, USA).
"Medication is available to prevent migraine but these treatments are
often secondary uses of the drug and come with potentially limiting
side-effects," noted Dr. Peter Goadsby of the UCSF Headache Center
and investigator in the study. "New therapies specifically developed
for migraine prevention are urgently needed especially for the
substantial proportion of migraine sufferers who have frequent
attacks and have significant disability in their daily lives.
Targeting mGluR5 signaling with ADX10059 is an interesting approach
that is showing significant promise in early clinical evaluation."
Preclinical experiments and small scale studies in migraineurs with
drugs like ketamine, which acts on glutamate signaling through NMDA
receptors (functionally related to mGluR5) and the NMDA antagonist
memantine, suggest that mGluR5 could play a role in the "migraine
circuit," a positive feedback loop that generates the symptoms of a
migraine attack. The initial step to test this hypothesis was Addex'
proof of concept study in acute treatment of migraine attacks.
In the Phase IIa trial of 129 migraine patients presented at ANN,
significantly more patients taking ADX10059 than those taking placebo
(16.7% vs 4.7%, respectively p = 0.039) were pain-free two hours
after dosing. ADX10059 administration yielded better pain improvement
than placebo at all time points up to two hours after treatment of a
migraine attack. In addition, there were trends to superiority for
ADX10059 over placebo for migraine pain improvement (mild or no pain)
at all time points up to two hours post-dosing.
"The clinical trial data for ADX10059, presented here at AAN, proved
the concept that by terminating acute attacks in some
patients, mGluR5 inhibition plays a role in migraine pathophysiology.
Now we are looking forward to the data from our ongoing Phase IIb
migraine prevention study in the first half of 2010," said Charlotte
Keywood, chief medical officer.
In December 2008, Addex initiated a Phase IIb trial to study ADX10059
as a prophylactic agent in migraine. The 12-week trial will compare
ADX10059 (25mg, 50mg or 100mg) versus placebo in migraine patients
who suffer three or more attacks per month. Data from the migraine
prevention trial are expected in the first half of 2010.
AAN Abstract P06.006: Investigation of the Role of mGluR5 Inhibition
in Migraine: A Proof of Concept Study of ADX10059 in Acute Treatment
of Migraine will be presented by Peter Goadsby, Director of the UCSF
Headache Center, San Francisco, and Charlotte Keywood, Chief Medical
Officer, Addex Pharma during Poster Session VI: Headache III in room
6E on Wednesday, April 29, 2009 4:00 PM. The authors are available
for interviews prior to and during the conference.
Migraine is a condition distinguished by recurrent episodes of a
characteristic headache, which can be accompanied by a variety of
other symptoms such as nausea, and sensitivity to light and sound.
The average migraine patient suffers 12 attacks a year. The
International Headache Society estimates that about 25% of migraine
patients have three or more attacks per month and could benefit from
migraine prevention treatment. A migraine attack, which typically
lasts about 24 hours but can range from 4-72 hours, has three
distinct phases: the prodrome phase, when an array of individual
warning signs - like blurred vision or tingling of the skin - may
begin to appear; the headache phase; and the postdrome phase, when
many patients report fatigue or other "hangover-like" symptoms. As
migraine attacks are prolonged, many patients and especially those
with frequent attacks, lose a significant amount of work and family
time to suffering caused by the disease. Indeed, migraine is
currently estimated to cost employers $13 billion annually in lost
productivity in the United States. Prevalence of migraine is
estimated at 12% in the United States, where about 30 million people
suffer from migraine. Given the role of glutamate in the
pathophysiology of migraine, the future of migraine prophylaxis, may
lie in modulating one of the receptors in the glutamate system,
mGluR5.
mGluR5 inhibition: Research has shown that glutamate is the major
neurotransmitter involved in the initiation and the propagation of
the migraine circuit, a positive feedback loop that leads to pain and
inflammation in the brain and hence migraine symptoms. mGluR5 is
known to be expressed in key brain regions involved in the migraine
circuit. Addex postulated that ADX10059 could interrupt the migraine
circuit to abort an active attack and potentially prevent an attack
from being triggered. ADX10059 has been shown by Addex to have a
superior effect to placebo in acute treatment of migraine headache in
Phase IIa testing. Inhibition of mGluR5 has therapeutic potential in
multiple indications because mGluR5 is involved in a variety of
functions in the central and peripheral nervous systems*. In addition
to migraine, mGluR5 inhibitors have achieved clinical proof of
concept in separate studies in patients with gastroesophageal reflux
disease (GERD), 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 and is in Phase IIb testing for the
treatment of GERD and, separately, migraine headache. Both are
important diseases for which existing products have established
multi-billion dollar markets despite sub-optimal efficacy. ADX10059
is a first-in-class mGluR5 inhibitor, a therapeutic strategy that
also is being pursued to treat multiple indications by large pharma
competitors.
Our product pipeline and technology already have proven their value
through our relationships with four of the top 10 pharmaceutical
companies in the world. Specifically, in two separate license
agreements with Merck & Co., Inc., we are developing positive
allosteric modulators of mGluR4 and mGluR5 as drugs to treat
Parkinson's disease and schizophrenia, respectively. A third
agreement, with Ortho McNeil Pharmaceuticals Inc., a Johnson &
Johnson company, is focused on development of positive allosteric
modulators of mGluR2 to treat anxiety and schizophrenia. Separately,
investment funds from Roche and GlaxoSmithKline have extended their
validation of our technology, products and management by making
significant investments in Addex.
Chris Maggos
Head of IR & Communications
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos@addexpharma.com
Disclaimer: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.
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