Addex drug candidate effective in osteoarthritis pain model
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Geneva, Switzerland, 13 July 2010 - Allosteric modulation company Addex
Pharmaceuticals Ltd. (SIX:ADXN) announced today that its preclinical drug
candidate ADX71943 was effective in a model of osteoarthritis pain. ADX71943 is
a potent and selective positive allosteric modulator of gamma-aminobutyric acid
subtype B (GABA-B) receptors. GABA-B receptors mediate the slow, prolonged
physiological effects of the inhibitory neurotransmitter GABA and are implicated
in pain processing. Phase I clinical testing is scheduled to start by the end
of 2010.
"We believe the allosteric mechanism of ADX71943 is the key factor in the
differentiated tolerability and lack of tolerance development observed in these
preclinical studies. We look forward to testing this compound in humans, where
we hypothesize that this product could provide not only a novel treatment for
osteoarthritis pain, but also an important opioid-sparing therapy for other
chronic pain indications," Addex CEO Vincent Mutel said.
The effects of ADX71943 on mechanical hyperalgesia (increased pain sensitivity)
and mechanical allodynia (pain produced by a normally innocuous stimulus) were
assessed in the monosodium iodoacetate (MIA) model of osteoarthritis, a model of
chronic nociceptive pain. ADX71943 significantly reduced mechanical hyperalgesia
and showed a trend toward reducing mechanical allodynia after both acute and
sub-chronic (8 days) dosing. Statistically significant antihyperalgesic activity
was observed on the first day and was maintained on day 8, despite increased
pain severity.
A maximal effect of ADX71943 was already achieved with the lowest dose tested (1
mg/kg). The efficacious plasma concentration (corresponding to 1 mg/kg) was
approximately 30-50 ng/mL. Importantly, no development of tolerance was observed
during the eight day treatment period.
Addex reported previously that ADX71943 is orally efficacious in rodent models
of inflammatory pain (formalin test and Complete Freund's Adjuvant-induced
hypersensitivity) and visceral pain (acetic acid-induced writhing). ADX71943
also displays an improved tolerability profile with reduced side effects
compared to baclofen.
Baclofen, a marketed generic orthosteric GABA-B receptor agonist, has shown
analgesic effects in animal models of inflammatory and neuropathic pain. There
also is some evidence of analgesic activity of baclofen in patients with
neuropathic and cancer pain, although its use in patients is limited by CNS side
effects.
Addex Pharmaceuticals (www.addexpharma.com) discovers and develops allosteric
modulators for human health and is focused on validated therapeutic targets for
diseases of the central nervous system, metabolic disorders and inflammation.
Subject to the completion of Phase I testing and regulatory approvals, Phase II
clinical trials are expected to start in 2010 in four indications for two lead
products: ADX48621, an mGluR5 negative allosteric modulator (NAM), in dystonia
and Parkinson's disease levodopa-induced dyskinesia (PD-LID); and ADX71149, an
mGluR2 positive allosteric modulator (PAM), in schizophrenia and anxiety.
ADX71149 is licensed to Ortho-McNeil-Janssen Pharmaceuticals Inc. In addition,
Merck & Co., Inc. has licensed rights to two preclinical products: mGluR4 PAM
for Parkinson's disease and mGluR5 PAM for schizophrenia. Additional preclinical
discovery stage programs include: mGluR2 NAM, GLP1R PAM, IL1R1 NAM and TNFR1
NAM. Roche Venture Fund and SR-One, corporate venture arm of GlaxoSmithKline,
are investors in Addex.
Chris Maggos
Investor Relations & Communications
Addex Pharmaceuticals
+41 22 884 15 11
chris.maggos(at)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.
[HUG#1431095]
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Addex Pharmaceuticals
12, chemin des Aulx Plan-les-Ouates; Geneva Switzerland
ISIN: CH0029850754;
Deutsch (pdf): http://hugin.info/138017/R/1431095/377691.pdf
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Datum: 13.07.2010 - 07:01 Uhr
Sprache: Deutsch
News-ID 23791
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