Addex's ADX48621 Effective in Preclinical Parkinson's Disease Studies
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Presented at the International Congress of Parkinson's Disease and Movement
Disorders
Geneva, Switzerland, 15 June 2010 - Allosteric modulation company Addex
Pharmaceuticals Ltd (SIX:ADXN) today presented encouraging data from preclinical
studies demonstrating the anti-Parkinson's effects of ADX48621, a novel drug
candidate that has completed three Phase I clinical trials.
Addex presented preclinical data at the 14(th) International Congress of
Parkinson's Disease and Movement Disorders held in Buenos Aires, Argentina
showing that ADX48621 was effective in two well-established models of PD: the
MPTP monkey model of Parkinson's disease levodopa induced dyskinesia (PD-LID)
and the rat haloperidol induced catalepsy (HIC) model of PD symptoms. Addex
previously disclosed that ADX48621, a negative allosteric modulator (NAM) of the
metabotropic glutamate receptor 5 (mGluR5), was effective in these models and
had achieved satisfactory pharmacokinetics, safety and tolerability in three
separate Phase I clinical trials in a total of 130 healthy volunteers, including
older subjects.
PD-LID develops in most PD patients after receiving levodopa for several years.
It is a complication caused by dopamine replacement therapy (i.e. levodopa). The
two main components of LID are chorea and dystonia. Chorea is manifest as sudden
rapid uncontrolled movements (e.g. jerking). Dystonia is manifest as slow
writhing type movements and sustained muscle contractions, which can be painful.
In the MPTP model of PD-LID, ADX48621 (30 mg/kg) statistically and significantly
inhibited LID. At this dose, ADX48621 almost abolished chorea and dystonia, the
two major components of LID, without affecting the beneficial effects of
levodopa as determined by disability scores.
In the rat HIC model of PD, ADX48621 decreased catalepsy time dose dependently,
by 19% 43%, 53%, and 65% at 1, 3, 10 and 30 mg/kg, respectively, compared to
vehicle control. There was a trend to efficacy at 3mg/kg, with statistical
significance at 10 (p < 0.01) and 30 mg/kg (p<0.001). These data show that the
minimal effective dose of ADX48621 was 10 mg/kg, with a corresponding plasma
concentration of about 1700 ng/ml.
"We are very encouraged by these data, particularly the effect of ADX48621 on
dystonia, a debilitating movement disorder in PD and also in other patients who
do not have PD. To our knowledge, no other drug on the market or in development
has demonstrated this level of activity in this primate model. Furthermore, the
data from the HIC model indicate that, in the long-run, ADX48621 also could be
tested as a treatment for the general symptoms of PD, potentially as a
complementary drug that would allow doctors to optimize levodopa dosing," noted
Charlotte Keywood, chief medical officer at Addex. "There is currently no
treatment approved for PD-LID and with the condition affecting so many people.
We look forward to starting Phase II testing of ADX48621 in PD-LID and dystonia
patients around the end of this year."
Parkinson's disease is a degenerative disease of the brain that often impairs
motor skills, speech, and other functions. It is estimated that 60,000 new cases
are diagnosed each year in the U.S., where more than 1.5 million people
currently have PD. While the condition usually develops after the age of
65, 15% of those diagnosed are under 50. PD affects both men and women in almost
equal numbers. Over time, generally several years, most PD patients treated with
levodopa develop PD-LID.
mGluR5 inhibition reduces signaling activity of the neurotransmitter glutamate.
Marketed blockbuster drugs treat multiple indications by targeting other types
of neurotransmitter signaling, including selecitive serotonin reuptake
inhibitors (SSRIs) used to treat depression and dopamine receptor inhibitors
used to treat schizophrenia. The rationale for using mGluR5 inhibition in PD is
that the loss of dopamine producing cells leads to excess glutamatergic
stimulation in the brain's "striatopallidal pathway". mGluR5 are found
abundantly in the striatum and are implicated in the excess glutamate activity
in Parkinson's Disease. Research shows that inhibition of glutamate stimulation
in this pathway has generated anti-Parkinsonian effects in animal models of PD
and PD-LID and in humans with PD-LID.
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. A third product, ADX71943, GABA-B
receptor PAM with potential for chronic pain, is scheduled to enter Phase I
testing around the end of 2010. 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#1424132]
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Addex Pharmaceuticals
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PDF: http://hugin.info/138017/R/1424132/372824.pdf
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Datum: 15.06.2010 - 18:00 Uhr
Sprache: Deutsch
News-ID 22487
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