Addex Reports Top-line Data from a Successful Phase 2a Clinical Study with ADX71149 in Schizophrenia Patients
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Addex Therapeutics /
Addex Reports Top-line Data from a Successful Phase 2a Clinical Study with
ADX71149 in Schizophrenia Patients
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* Key objectives achieved
* Safety and tolerability demonstrated
* Sub population identified for potential treatment with ADX71149
* ADX71149 dose with optimal benefit / risk identified
Geneva, Switzerland, 5 November 2012 - (SIX:ADXN), a leading company pioneering
allosteric modulation-based drug discovery and development, announced today top-
line data from a successful Part B of the first-in-patient Phase 2a clinical
study of ADX71149 in schizophrenia, that was conducted by Janssen Research &
Development, LLC, on behalf of its affiliate Janssen Pharmaceuticals Inc. The
data show that ADX71149 met the primary objectives of safety and tolerability.
ADX71149 also demonstrated an effect in patients with residual negative
symptoms. The 50mg b.i.d. dose was identified as having the optimal benefit/risk
ratio in this study.
ADX71149 is an oral, selective, small molecule, positive allosteric modulator
(PAM) of the metabotropic glutamate receptor 2 (mGluR2), a Class C G-Protein
Coupled Receptor (GPCR), with potential to be used in the treatment of
schizophrenia and the treatment of anxiety in patients suffering from major
depressive disorder.
This first-in-patient study is being conducted in the EU, to determine the
safety and tolerability of ADX71149 and to explore the potential clinical effect
of this mGluR2 PAM in patients with schizophrenia. The study has two concurrent
parts (A and B) and is designed to identify the patient populations most likely
to benefit from treatment with ADX71149.
Part A: Safety, tolerability and efficacy of ADX71149 as monotherapy in the
treatment of patients with sub-acute psychosis. This is a 12 week open-label
treatment in 15 patients not on antipsychotic medication. Dose range from 50 mg
b.i.d titrated up to 150 mg b.i.d. Part A is ongoing.
Part B: ADX71149 as adjunctive therapy to antipsychotics. This part of the study
for which top-line data are being reported today, was a randomised double-blind,
placebo-controlled trial designed to evaluate the safety, tolerability and
exploratory efficacy of ADX71149, in 92 patients who were on stable doses of
antipsychotic medication. The study population comprised 3 groups: patients with
residual negative symptoms (n = 47); patients with residual positive symptoms (n
= 25); and patients with insufficient response to clozapine treatment (n = 20).
For the first 4 weeks of treatment all patients were randomised to receive
either ADX71149 50 mg b.i.d, ADX71149 150 mg b.i.d or placebo, taken
concomitantly with their currently prescribed antipsychotic medication
(randomized 2:2:1).
"I am delighted that the study achieved its objectives of demonstrating good
safety and tolerability and identifying the population of schizophrenia patients
most likely to benefit from adjunctive treatment with ADX71149," noted Dr.
Charlotte Keywood, CMO at Addex.
Negative symptoms (typically comprising apathy, social withdrawal, loss of
emotional expression and sleep disorders) are common, and occur in up to 90% of
patients with schizophrenia. Currently available drugs do not always provide
effective control and many patients remain with substantial disability as a
result. Therefore, effective treatment of negative symptoms is a major unmet
medical need in the management of schizophrenia.
"We are extremely proud of our partnership with Janssen and greatly appreciate
their continued commitment towards advancing ADX71149 and our mGluR2 PAM program
in these psychiatric indications with significant unmet medical need," said Dr.
Bharatt Chowrira, CEO at Addex. "These top-line results are a significant
achievement for Addex and serve as further validation for our innovative oral
small molecule allosteric modulation drug discovery technology platform."
The development of ADX71149 is part of a worldwide research collaboration and
license agreement between Addex and Janssen Pharmaceuticals Inc. to discover,
develop and commercialize novel mGluR2 PAM for the treatment of anxiety,
schizophrenia and other undisclosed indications. Under the terms of the
agreement, Addex is eligible for up to a total of ?112 million in milestone
payments upon potential development and regulatory achievements. In addition,
Addex is eligible for low double-digit royalties on sales of mGluR2 PAM
developed under the agreement.
About mGluR2PAM
Glutamate is a powerful transmitter in the brain and integral to the normal
functioning of memory, learning and perception. Too much glutamate can lead to
seizures and the death of brain cells. Too little glutamate can cause psychosis,
coma and death. Glutamate exerts these effects by interacting with many
receptors in the brain, especially NMDA and AMPA receptors. In addition to these
primary receptors, glutamate triggers other receptors, termed metabotropic
because they adjust the amount of glutamate that cells release rather than
simply turning glutamate transmission on or off. In addition, there are eight
types of metabotropic glutamate receptors (mGluR), each with different
functions. Thus, these mGluRs, because of their ability to fine-tune glutamate
signaling, appear to be attractive targets for drug treatment. Indeed, industry
has been investing in mGluR research for about three decades and research shows
that mGluR drugs have potential for the treatment of schizophrenia, anxiety,
Parkinson's disease, fragile X syndrome, Alzheimer's disease, depression and
post-traumatic stress disorder. The effects of positive allosteric modulators of
mGluR2 are independent of dopamine receptors, indicating the potential for
mGluR2 modulators to offer efficacy while avoiding the side effects associated
with market leading antipsychotic drugs which appear to work predominantly via
their effects on dopamine receptors. Furthermore, mGluR2 activation has shown
efficacy in patients suffering from schizophrenia and, separately, anxiety.
About Schizophrenia
Schizophrenia is a chronic progressive highly disabling and distressing disease
which affects the way patients perceive the world around them, and profoundly
decreases their ability to function normally. Symptoms are divided into three
categories, positive, negative and cognitive. Positive symptoms reflect an
excess or distortion of normal functions (delusions, hallucinations, thought
disorder and disorganized behavior. Negative symptoms refer to a diminishment or
absence of characteristics of normal function, and may appear with or without
positive symptoms. Negative symptoms include loss of interest in everyday
activities, appearing to lack emotion, reduced ability to plan or carry out
activities, neglect of personal hygiene, social withdrawal and loss of
motivation. Cognitive symptoms involve problems with thought processes and may
be the most disabling in schizophrenia because they interfere with the ability
to perform routine daily tasks. As a result, schizophrenia patients often
withdraw from society and are unable to support themselves. The prevalence of
schizophrenia is estimated at about 1% of the population worldwide. The
prevalence of negative symptoms in first-episode psychosis is high, 50-90%, and
20-40% of schizophrenia patients have persisting negative symptoms. Estimates of
the costs to society from schizophrenia run at approximately $65 billion per
year in the United States, despite the use of antipsychotic drugs.
Notwithstanding their over $15 billion in annual sales, not all of the currently
marketed antipsychotic drugs fully address the negative symptoms of
schizophrenia, such as anxiety, depression and cognitive dysfunction. In
addition, marketed antipsychotic drugs may cause side effects, including
sedation, extrapyramidal symptoms (impairment of control of movements), hormonal
imbalances leading to hyperprolactinemia and weight gain.
Addex Therapeutics (www.addextherapeutics.com) discovers and develops an
emerging class of small molecule drugs, called allosteric modulators, which have
the potential to be more specific and confer significant therapeutic advantages
over conventional "orthosteric" small molecule or biological drugs. The Company
uses its proprietary discovery platform to address receptors and other proteins
that are recognized as attractive targets for modulation of important diseases
with unmet medical needs. The Company's two lead products are being investigated
in Phase 2 clinical testing: dipraglurant (ADX48621, an mGluR5 negative
allosteric modulator or NAM) is being developed by Addex to treat Parkinson's
disease levodopa-induced dyskinesia (PD-LID); and ADX71149 (mGluR2 positive
allosteric modulator or PAM) is being developed in collaboration with Janssen
Pharmaceuticals Inc. to treat schizophrenia and anxiety seen in patients
suffering from major depressive disorder. Addex also is advancing several
preclinical programs including: GABA-BR PAM for spasticity in MS, OAB and other
disorders; mGluR4 PAM for Parkinson's, MS, anxiety and other diseases. In
addition, Addex is applying its proprietary discovery platform to identify
highly selective and potent allosteric modulators of a number of both GPCR and
non-GPCR targets that are implicated in diseases of significant unmet medical
need.
Tim Dyer
Chief Financial Officer
Addex Therapeutics
+41 22 884 15 61
PR(at)addextherapeutics.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
Therapeutics, formerly known as, Addex Pharmaceuticals, 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 Therapeutics 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, GABA-BR 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, GABA-BR or other therapeutics
targets 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, GABA-BR 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, GABA-BR 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 Therapeutics 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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(ii) they are solely responsible for the content, accuracy and
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Source: Addex Therapeutics via Thomson Reuters ONE
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Datum: 05.11.2012 - 07:00 Uhr
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