Addex Reports Top-line Data from a Successful Phase 2a Clinical Study with ADX71149 in Schizophrenia Patients
• 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@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.
Posted: November 2012
