CNS Drug News

Issue No. 167 2nd August 2007

R&D Highlights Will discovery be a breakthrough

for MS?
Compound reverses signs of AD
The end of July has seen a major genetic advance made in multiple
Page 4 sclerosis (MS) - the identification of a new gene, a functional variant
of which has been associated with an increased susceptibility to
TBZ protects brain cells in HD model the disease. Dr Simon Gregory, of Duke University Medical Center,
Page 8 believes that the finding is important because the genetic factors
that are already known to be associated with MS only explain less
than half of the total genetic basis for the disease. While it has been
deCODE discovery points to new RLS treatment approach known that there is a strong genetic basis for MS, only genes within a
Page 10 region of chromosome 6 have, to date, been implicated in the disease.
However, the functional gene variant identified in the new research is
Study may accelerate research into next generation of on chromosome 5.
painkillers This will be good news for the approximately 2.5 million people
Page 15 worldwide affected by MS; the risk of developing MS amongst the
general population is approximately 110 in 100,000, however, the
prevalence may be higher because of the uncertainty in diagnosing
PRODUCT Highlights the disease, which is the most common cause of neurological disability
in young adults. Importantly, it is thought that the research may lead to
GW withdraws European application for Sativex in MS novel treatments for the disease or the identification of targets for new
therapies for the MS market, which was estimated to be worth US$4.9
spasticity billion in 2006, with a growth rate of 8.9 per cent year on year, and is
Page 6 the fifth largest segment of the CNS market (source: Espicom's CNS
Drug Discoveries - What The Future Holds).
Organon’s MAA for sugammadex accepted for review
It remains to be seen whether this discovery has the impact on MS
Page 16 research that its coverage has suggested and it should be noted
that variants of many genes are thought to be associated with the
CHMP recommends upgraded warnings for Acomplia development of the disease. Nevertheless, identifying a novel gene
Page 19 that is associated with MS will undoubtedly help in understanding this
complex disease.

AGREEMENT Highlights In other news, scientists at deCODE genetics, in collaboration with

Eisai enters partnership for Sepracor’s eszopiclone
Page 11
GSK forms US$1.5 billion CNS pact with Targacept
colleagues from Emory University, have discovered the first variant in
the sequence of the human genome ever linked to risk of restless legs
syndrome (RLS) and periodic limb movements (PLMs). The SNP was
associated with an increased risk of RLS with PLMs of 70 to 80 per cent
for those who carry one copy, compared to those without the variant,
and is believed to account for approximately 50 per cent of cases.

Page 20 The discovery provides new evidence that RLS is a genuine disease
with an identifiable biological basis, a fact that has recently been
EDITOR the subject of some debate. Indeed, in April last year, CNS Drug News
Lucy Vann published an editorial questioning whether the pharma industry
had been exaggerating the prevalence of RLS (see CNS 136). The new
CONTRIBUTING EDITORS
research will be welcomed by the drug companies, particularly those
Ros Smallman, Fiona Cowie, with products either marketed or in development for the condition,
Matthew Dennis, Johanna Shiu, Sam Turner such as Boehringer Ingelheim, which saw the FDA approve Mirapex
PUBLISHER (pramipexole) for the treatment of moderate-to-severe primary RLS in
Eric Wigart November last year.
Conditions of Sale
• CNS Drug News must not be reproduced, abstracted, stored in a retrieval system Lucy Vann
or transmitted in any form or by any means without the written permission of the Editor
publisher. pharma_editorial@espicom.com
• CNS Drug News must not be circulated to staff outside the address to which it is sent.
ISSN 1462-656X THE NEXT ISSUE OF CNS DRUG NEWS WILL BE
©
Espicom Business Intelligence. All rights reserved. PUBLISHED ON 23RD AUGUST 2007

Monitoring central nervous system drug developments worldwide

TABLE OF CONTENTS
TABLE OF CONTENTS
Will discovery be a breakthrough for MS?.............................................................................1
NEURODEGENERATIVE DISORDERS.......................3
Parkinson's Disease - R&D Update........................................................3
Enrolment on target in Phase III trial of PD-02......................................................................3
Phase III PD data for safinamide delayed..............................................................................3
Proximagen awarded MJFF grant to pursue gene therapy approach for PD......................3
VASTox re-named as Summit.................................................................................................3
Alzheimer's Disease - R&D Update........................................................3
Cortex to resume enrolment in CX717 study at all dose levels.............................................3
Affiris begins clinical testing of AD vaccine...........................................................................4
Researchers shed light on how diet and exercise enhance longevity..................................4
AstraZeneca initiates Phase IIb trial of AZD3480 in AD.........................................................4
Compound reverses signs of AD.............................................................................................4
Neurochem granted fast track designation for Alzhemed...................................................5
Product News........................................................................................5
Novartis' Exelon patch recommended for European approval............................................5
Agreement News...................................................................................6
Neuroptix receives milestone payment from Merck in AD collaboration............................6
Multiple Sclerosis - R&D Update..........................................................6
Research identifies first new MS gene in 30 years................................................................6
Nuon raises funds to advance tranilast development..........................................................6
BioMS' RRMS trial receives positive DSMB review................................................................6
Product News........................................................................................6
GW withdraws European application for Sativex in MS spasticity......................................6
Agreement News...................................................................................7
Glenmark purchases rights to CHR-1103 and CHR-1201 from Chromos..............................7
Nuon and Kissei complete tranilast agreement....................................................................8
Other Neurodegenerative Disorders - R&D Update...........................8
TBZ protects brain cells in HD model.....................................................................................8
Avicena to proceed with confirmatory Phase III ALS trial.....................................................8
First patient treated in Phase II trial of Dimebon for HD.......................................................8
Intellect reports positive safety data from Phase Ia Oxigon trial.........................................9
Product News........................................................................................9
Neurochem receives second FDA approvable letter for Kiacta in AA amyloidosis..............9
Rilutek patent ruled not invalid.............................................................................................9
Agreement News...................................................................................9
Biogen Idec to exercise first milestone investment in ALS collaboration with Amorfix.....9
Tikvah/Academia Sinica enter licensing agreement for neurodegenerative disorders.....9
Cerebrovascular Disorders..........................10
R&D Update.............................................................................................10
SYGNIS completes Phase IIa study of AX200 in stroke..........................................................10
Anxiolytics/Sleep Disorders..........................10
R&D Update.............................................................................................10
deCODE discovery points to new RLS treatment approach..................................................10
Severe trauma may affect children's brain function.............................................................10
Product News........................................................................................11
Sepracor submits Lunivia MAA..............................................................................................11
Caraco receives tentative FDA approval for generic Provigil................................................11
Agreement News...................................................................................11
Eisai enters partnership for Sepracor's eszopiclone..............................................................11
Antidepressants.............................................12
R&D Update.............................................................................................12
Add-on mecamylamine treatment shows positive effects in depression..........................12
Product News........................................................................................12
Abilify sNDA granted priority review by FDA.........................................................................12
Biovail receives non-approval letter from FDA for BVF-033.................................................12
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CNS Drug News
Psychotic Disorders.......................................12
R&D Update.............................................................................................12
BL-1020 shows antipsychotic efficacy; enters Phase II trial in schizophrenia......................12
Drug may help people with OCD; to be tested on smokers..................................................13
Children show sustained improvement after ADHD treatment...........................................13
Progressive grey matter loss discovered in BPD....................................................................14
Product News........................................................................................14
EMEA recommends authorisation of first generic medicine for human use.......................14
Shire's Vyvanse available in US pharmacies..........................................................................14
Analgesics/Anaesthetics................................15
R&D Update.............................................................................................15
Study may accelerate research into next generation of painkillers.....................................15
Durect reports positive Phase IIb Posidur data.....................................................................15
Newron reveals additional analyses of ralfinamide Phase II study......................................15
Meda agrees to acquire MedPointe.......................................................................................16
Akela completes enrolment in Phase IIb trial of Fentanyl TAIFUN.......................................16
Product News........................................................................................16
Ortho-McNeil/Par settle Ultracet patent litigation...............................................................16
Organon's MAA for sugammadex accepted for review........................................................16
RxElite launches generic sevoflurane in the US.....................................................................16
US PTO allows Opana ER-related patent application............................................................16
Agreement News...................................................................................16
Hydra signs global TRPV3 collaboration with Pfizer..............................................................16
Tikvah enters licensing agreement with Apkarian...............................................................17
Therapies to Treat Substance Dependence....17
R&D Update.............................................................................................17
Nabi creates pharmaceuticals business unit.........................................................................17
Drug may help people with OCD; to be tested on smokers..................................................17
Product News........................................................................................17
UK's NICE issues guidance on Champix for smoking cessation.............................................17
Anti-Epileptics................................................17
R&D Update.............................................................................................17
Icagen files IND for novel epilepsy compound......................................................................17
Eating Disorders.............................................18
R&D Update.............................................................................................18
Preclinical data confirm trodusquemine's potential for obesity..........................................18
Orexigen reports positive Phase IIb data with Empatic for obesity.....................................18
Product News........................................................................................19
CHMP recommends upgraded warnings for Acomplia........................................................19
Drugs used in Nausea & Vertigo.....................19
Agreement News...................................................................................19
Shanghai Ethypharm signs ondansetron licence agreement with Beijing Med-Pharm....19
General Development News...........................19
R&D Update.............................................................................................19
Study further links addiction and memory...........................................................................19
Targacept/Abbott initiate Phase I trials of NNR modulators................................................19
Agreement News...................................................................................20
Corcept enters microdosing study agreement with Xceleron..............................................20
Penwest/Edison enter collaboration for neurological disorders.........................................20
Antares signs product development and licence agreement with Jazz..............................20
GSK forms US$1.5 billion CNS pact with Targacept...............................................................20
Conference Listings........................................21
COMPANY INDEX.................................................22
Compound INdex..............................................23
2nd August 2007
CNS Drug News
NEURODEGENERATIVE DISORDERS
Parkinson's Disease - R&D Update
Enrolment on target in Phase III trial of PD-02
The Phase III efficacy trial of Avicena Group's lead Parkinson's disease
(PD) drug candidate, PD-02 (creatine), has enrolled 288 patients in
the first three months. The study, which is sponsored by the National
Institute of Neurological Disorders and Stroke (NINDS), is evaluating
PD-02's potential to slow the progression of PD.
This trial will enrol over 1,720 patients at more than 50 sites in the US
and Canada, making it one of the largest PD trials ever conducted.
Avicena previously announced that the NINDS had awarded a grant
for the study. As part of the company's collaboration with the NINDS,
Avicena will supply PD-02 and placebo for use in the trial. In return,
Avicena will have access to the study's data to file an NDA with the FDA
for the approval of PD-02 as a treatment for PD. Avicena also holds
intellectual property rights for the use of PD-02 in PD.
Data from Phase II efficacy trials conducted at the University of
Rochester showed PD-02 to be safe and well tolerated. Furthermore,
findings demonstrated the compound's potential to slow the rate of
disease progression, as measured by the UPDRS. In preclinical studies
of PD, PD-02 demonstrated significant neuroprotective properties,
including protection of the dopaminergic cells that are affected in the
disease.
Phase III PD data for safinamide delayed
Newron Pharmaceuticals has confirmed that the disclosure of data
from a 12-month extension of a Phase III trial with safinamide, an
orally-administered alpha-aminoamide derivative, in early Parkinson's
disease (PD) patients will be delayed; the information had been
expected by the end of June. Merck Serono (Merck KGaA) has exclusive
worldwide rights to develop, manufacture and commercialise
safinamide in PD, Alzheimer's disease, other cognitive disorders and
restless legs syndrome.
Proximagen awarded MJFF grant to pursue gene
therapy approach for PD
Proximagen Neuroscience has been awarded a Novel Approaches
to Drug Discovery for Parkinson's Disease grant by the Michael J Fox
Foundation (MJFF) for Parkinson's Research to pursue research into
the development of a novel gene therapy approach for the treatment
of Parkinson's disease (PD).
The MJFF is providing the funding under an initiative established
through leadership funding from Elan. Under the terms of the
agreement, Elan is given a first option to obtain an exclusive
worldwide commercial licence to the programme.
The funding is to continue Proximagen's PRX4 research and
development programme, which centres around a gene that
produces a neuroprotective protein present in healthy individuals, but
lacking in patients with PD. PRX4 is being developed using viral vector
delivery technology, which delivers genetic material directly into brain
cells. The combined neuroprotective gene and viral vector will be
targeted to an area of the brain that degenerates in PD. If successful,
the treatment may prevent the disease from causing further damage
2nd August 2007 ©
Espicom Business Intelligence
NEURODEGENERATIVE DISORDERS
and could restore normal brain function to patients, reversing the
difficulties in movement that characterise this illness. Proximagen's
preclinical studies have shown that this neuroprotective protein is
implicated in the control of many mechanisms associated with the
degeneration of neurons. The company has demonstrated that even
in very low concentrations, PRX4 derivatives act as highly-potent
inhibitors of neurodegeneration in neuronal cells.
VASTox re-named as Summit
VASTox has changed its name to Summit. The new name, which was
approved by shareholders on 19th July, is aimed at encapsulating the
company's ambitions, as well as providing an identity that has the
flexibility to accommodate the future growth and development of the
business.
The company's lead drug candidates, which are in Phase I testing
for sialorrhoea and seborrhoea in Parkinson's disease, respectively,
will now be known as SMT D001 (formerly DL06001) and SMT
D002 (formerly DL06003). The new names for Summit's preclinical
candidates are: SMT C1100 (formerly VOXC 1100), for Duchenne
muscular dystrophy; SMT D003 (formerly DL06005), for glaucoma; and
SMT 14400 (formerly VOX 14400) for cancer.
Alzheimer's Disease - R&D Update
Cortex to resume enrolment in CX717 study at all dose
levels
Following a review of the Ampakine CX717 data package sent to the
FDA's Division of Neurology Products (DNP) on 17th April, the Agency
has given Cortex Pharmaceuticals the go-ahead to immediately
resume enrolment in the CX717 Alzheimer's disease (AD) PET scan
study at all requested dose levels. The study was originally designed
with doses of 200, 600 and 1,200mg to be administered to patients,
however, the FDA previously limited the dose levels such that the 600
and 1,200mg doses could not be administered. The new protocol
approved by the Agency allows a return to the original dose levels.
This double-blind study will attempt to determine if Cortex can
duplicate the PET scan findings in non-human primates, which
correlated with increased cognitive performance. The study is being
performed in mild-to-moderate AD patients who are drug naïve or
stabilised on cholinesterase inhibitors at the University of Michigan
Medical Center. In animal studies, cholinesterase inhibitors such as
Aricept (donepezil) and Reminyl (galantamine) appear to enhance the
effects of CX717.
The earlier dose limitations imposed by the FDA were related to
concerns over data from preclinical studies rather than any findings
from clinical trials. The DNP plans to continue its review of the data
package, but saw no reason to not permit the full resumption of
the current AD PET scan study. Cortex will continue to have further
discussions with the DNP regarding the previously-submitted
toxicology package and additional requirements may be requested
by the FDA.
Cortex intends to file a second IND for CX717 with the Division of
Psychiatry Products during the third quarter of 2007, to allow the
company to initiate a Phase IIb study evaluating the compound for the
treatment of attention deficit hyperactivity disorder.
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NEURODEGENERATIVE DISORDERS
Affiris begins clinical testing of AD vaccine
Affiris' Alzheimer's disease (AD) vaccine, Affitope AD01, has entered
the clinical phase of its development. Up to 24 patients with AD
are to be vaccinated, with the aim of this initial Phase I trial being to
demonstrate the vaccine's safety and suitability for human use.
Affiris has developed the vaccine from patented Affitope technology,
which is based on mimotopes and allows customised vaccines to be
manufactured cost-effectively. The company's approach protects
brain cells and only combats the disease-causing amyloid beta.
The vaccine is being administered at the Vienna General Hospital in
Austria, to patients who have reached the mild-to-moderate disease
stage. Patients will be vaccinated four times over a period of three
months, and the safety and suitability of the vaccine will be analysed
over six months.
Researchers shed light on how diet and exercise
enhance longevity
Through studying long-lived mice, Howard Hughes Medical Institute
researchers at Children's Hospital Boston and Harvard Medical School
have found that sensible diet, exercise and weight control extend
life by reducing signalling through a specific pathway in the brain.
The investigators, whose work was published in the 20th July issue
of PNAS (2007;317:369-372), believe that their findings underscore
the importance of maintaining a healthy lifestyle and may also
offer promising research directions for understanding and treating
Alzheimer's disease (AD) and diabetes.
The insulin-like signalling pathway is known to govern growth and
metabolic processes in cells throughout the body. The pathway is
activated when insulin and insulin-like growth factor-1 switch on
insulin receptor substrates (Irs). Other researchers had shown that
reducing the activity of the pathway in Caenorhabditis elegans and
Drosophila extends lifespan, however, based on previous work, the
team thought that more of the lrs, Irs2, in liver and pancreatic beta
cells would be beneficial. lrs2 reduces the amount of insulin needed in
the body to control blood glucose, plus it promotes growth, survival
and insulin secretion from beta cells.
In earlier work, the researchers had found that knocking out both
copies of the Irs2 gene in mice reduces brain growth and produces
diabetes due to beta cell failure. However, in the new study, when the
researchers knocked out only one copy of the gene, they found that
the mice lived 18 per cent longer than normal mice.
Because reducing insulin-like signalling in the neurons of roundworms
and fruitflies extends their lifespan, the researchers decided to
examine what would happen if one or both copies of the Irs2 gene
were knocked out only in the brains of mice.
Mice lacking one copy of the Irs2 gene in brain cells also showed an
18 per cent longer lifespan and the near complete deletion of brain
Irs2 had a similar effect. Further, the animals lived longer, even though
they had characteristics that should shorten their lives, including being
overweight, hyperinsulinaemic and glucose intolerant. However,
both sets of Irs2-knockout mice exhibited other characteristics that
marked them as healthier. They were more active as they aged and
after eating, the animals' brains showed higher levels of the potent
antioxidant enzyme, superoxide dismutase.
These findings put a mechanism behind what is already known, that
eating a good diet and exercising will keep a person healthy; diet,
exercise and lower weight keep peripheral tissues sensitive to insulin.
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CNS Drug News
This reduces the amount and duration of insulin secretion needed
to keep glucose under control after eating, therefore, the brain is
exposed to less insulin. Since insulin turns on Irs2 in the brain, that
means lower Irs2 activity, which the researchers have now linked to
longer lifespan in the mouse.
The investigators are planning subsequent studies to better
understand how healthy ageing and lifespan are co-ordinated by
Irs2 signalling pathways in the body and brain. Scientists now have
a greater appreciation that obesity, insulin resistance and high
blood insulin levels are connected to AD, Huntington's disease and
dementias in general. These researchers speculate it is possible that
in people who are genetically predisposed to these disorders, too
much insulin overactivates Irs2 in the brain and accelerates disease
progression. Thus, insulin resistance and higher insulin levels might be
the environmental influences that promote these diseases.
AstraZeneca initiates Phase IIb trial of AZD3480 in AD
Targacept's strategic collaborator, AstraZeneca, has initiated a Phase
IIb trial of AZD3480 (TC-1734) in Alzheimer's disease (AD).
This double-blind, placebo-controlled study is being conducted at
sites in Western and Eastern Europe, as well as Canada. The trial design
provides for approximately 500 patients with mild-to-moderate AD
to be randomly assigned to one of three dose groups of AZD3480, an
active comparator or placebo, and to be dosed over a 12-week period.
The trial is expected to complete by the end of 2008.
AZD3480 acts selectively on neuronal nicotinic receptors (NNRs) and
has been evaluated in 12 clinical trials in approximately 540 subjects.
In a previous Phase IIb trial conducted by Targacept in age-associated
memory impairment, AZD3480 achieved statistically significant results
on all of the primary endpoints, demonstrating cognitive-enhancing
effects in memory-impaired older adults. Furthermore, AstraZeneca is
scheduled to begin dosing in a Phase IIb trial of AZD3480 for cognitive
deficits in schizophrenia in August.
For details of further NNR research and a collaboration by Targacept,
see Antidepressants, R&D Update; General Development News, R&D
Update; and General Development News, Agreement News.
Compound reverses signs of AD
Biologists at the University of St Andrews in the UK have developed a
compound, which is capable of blocking a nerve cell interaction that
is known to lead to the symptoms of Alzheimer's disease (AD), as well
as shown that it is possible to reverse some of the signs associated
with the disease. Dr Frank Gunn-Moore's team, in collaboration with
Columbia University researchers in the US, successfully reversed a sign
for the progression of AD and prevented the death of brain cells.
In AD, the amyloid protein inflicts damage by interacting with an
enzyme called ABAD (amyloid beta alcohol dehydrogenase) and
releasing toxic substances that kill brain cells. Gunn-Moore's research,
which was published in the June issue of Molecular and Cellular
Neuroscience (2007;35:377-382) and carried out in the laboratory using
a model of the disease, initially focused on developing the 3D shape of
ABAD and understanding how amyloid attaches itself to the structure.
Patients with AD produce too much amyloid and ABAD in their brains.
Based on their knowledge of ABAD, the researchers produced an
inhibitor that can prevent amyloid attaching to it in a living model and
showed that it is possible to reverse some of the signs associated with
the disease.
2nd August 2007
CNS Drug News
The work is now being continued to try and refine the inhibitor into
a potential drug. According to Gunn-Moore, the research holds a
possible key for the treatment of AD, particularly in its early stages. The
Alzheimer's Research Trust has awarded the St Andrews team a further
grant to develop the research over the next three years.
Neurochem granted fast track designation for
Alzhemed
The FDA has designated Neurochem's investigational product
candidate, Alzhemed (tramiprosate), as a fast track product for the
treatment of Alzheimer's disease.
As previously reported, Neurochem requested a meeting with
the FDA, which is now scheduled for August, with the Division of
Neurology Products. The goal of this meeting is to have a discussion
on the tramiprosate Phase III programme and present an update on
the work accomplished, to date, on the North American Phase III trial.
Neurochem will also seek the FDA's feedback and validation on the
next steps that would be acceptable to the Agency, especially with
respect to the statistical models.
In relation to the ongoing European Phase III trial, patient screening
activities will stop in August, as Neurochem has exceeded its original
patient enrolment objectives. However, in light of the information
and experience gained from the North American trial, the company
is presently considering modifications that would need to be made to
the design of the European study.
Product News
Novartis' Exelon patch recommended for European
approval
A patch that delivers Novartis' Exelon (rivastigmine) has received
a positive opinion for treating mild-to-moderately severe forms
of Alzheimer's disease (AD) from the EMEA's CHMP and the EC is
expected to issue a decision on the product within three months.
Since 1997, Exelon has been used to treat mild-to-moderate AD in
more than 70 countries. The FDA approved Exelon Patch on 6th July,
for the treatment of both mild-to-moderate AD and Parkinson's
disease dementia. The EU positive opinion was based on results
from the international IDEAL (Investigation of Transdermal Exelon
in ALzheimer's disease) trial, which showed that patients receiving
the patch demonstrated improved memory, overall functioning
and ability to perform everyday activities compared to those taking
placebo.
The patch is applied to the back, chest or upper arm, and provides
smooth and continuous delivery of medication through the skin over
24 hours, with the potential for improved efficacy. A key attribute
of the patch is a sharp reduction in gastrointestinal side effects
commonly seen with oral forms of the cholinesterase inhibitor class
of drugs. In a clinical trial, these side effects were greatly reduced,
with three-times fewer reports of nausea and vomiting than with the
capsule form of the drug.
Designed with compliance in mind, the patch was preferred to
capsules by >70 per cent of caregivers in a clinical study as a method of
drug delivery because it helped them follow the treatment schedule,
interfered less with their daily life and was easier to use overall than an
oral medication.
2nd August 2007 ©
Espicom Business Intelligence
NEURODEGENERATIVE DISORDERS
Clinical Biomarkers Forum
Harnessing the potential of biomarkers from translational
research, throughout clinical trials
13th – 14th September 2007, Prague
Delegates already attending have brought their queries to the
table, and will benefit from case study presentations and
roundtable discussions on:
ƒ Maximising the potential of biomarkers across drug
development
ƒ How companies have lowered attrition, risk and costs
ƒ Development of surrogate biomarkers and companion
diagnostics for the pharmaceutical industry
ƒ How can we translate pre-clinical results into humans?
ƒ Have companies seen a real reduction in timeframes as a
direct result of biomarker implementation?
ƒ When will regulations catch up with innovation?....And
much more!
What is your number one concern or question relating to the
performance of biomarkers in R&D? Make sure that it is raised
and answered at this unique event by registering today.
To download a brochure, visit our website at:
www.clinicalbiomarkers.net
Our expert panel of speakers includes:
x Dr Stefan Scherer, Biomarker Program Leader, AVASTIN, F.
Hoffmann-La Roche
Dr. Stefan Sultana, Translational Medicine Leader for GU
Therapeutic Area, Pfizer
x Dr. Orest Hurko, Assistant Vice President, Translational
Research, Wyeth
Clavert Louden, Head, Department of Pathology Assessment,
AstraZeneca
x Dr. Thomas Senderovitz, Vice President Global Clinical
Pharmacology & Experimental Medicine, UCB Pharma S.A.
x Dr. Chetan Lathia, Director, Global Clinical Pharmacology,
Bayer
x Dr. Stefan Otto Muller, Senior Toxicologist, Merck Serono
KGAA
x Dr. Eric Blomme, Project Leader, Cell and Molecular
Toxicology, Abbott
TO REGISTER YOUR PLACE
Go online at www.clinicalbiomarkers.net
or
Contact Paul Osmond: +44 (0)20 7880 0000
Email: paul_osmond@osneymedia.co.uk
Page 
NEURODEGENERATIVE DISORDERS
Agreement News
Neuroptix receives milestone payment from Merck in
AD collaboration
Neuroptix has been granted a US$1 million milestone payment under
its Alzheimer's disease (AD) diagnostic collaboration with Merck
& Co. Under the agreement, which was announced in December
2006, Neuroptix provides Merck with access to its laser eye-scanning
technologies, which in preclinical studies, have detected AD-related
amyloid protein aggregates in the lens of the eye. The quantitative
technique has potential for the early detection and monitoring of AD
progression.
Multiple Sclerosis - R&D Update
Research identifies first new MS gene in 30 years
A gene has been identified that may hold the promise of guiding
future research into therapies for multiple sclerosis (MS). According
to its discoverers, this is the first major genetic advance in 30 years for
understanding the disease.
The finding, which was published in the 29th July online edition of
Nature Genetics (10.1038/ng2103), demonstrates that a functional
gene variant on chromosome 5 was associated with an increased
susceptibility to the disease. The gene increases an individual's risk of
MS by 30 per cent and this variant has an effect on the function of the
gene.
First author, Dr Simon Gregory, and his colleagues at Duke University
Medical Center were joined by researchers from the University of
California, San Francisco and the University of Cambridge in the UK,
who spearheaded the collection of MS populations over many years,
and the University of Miami and Vanderbilt University. The same team
was also involved in another paper replicating similar findings from a
whole-genome analysis, which was published in the 29th July online
edition of the NEJM (10.1056/NEJMoa073493).
Previously-discovered MS genes were all located in an area of
chromosome 6 involved in the major histocompatibility complex.
The gene variation discovered in the new research is located on
chromosome 5 and involved in guiding the production of interleukin-
7 receptor alpha (IL-7R), which is a critical receptor for the development
and growth of key immune system cells.
The scientists used the technique of genomic convergence, in which
they took the results of many studies looking for common elements.
From studies involving patients and their families in the US and UK,
they analysed more than 7,000 DNA samples from patients with
confirmed MS and those without the disease.
After winnowing down 28 candidate genes to the IL-7R gene, the
researchers then tested their findings on a different set of patient
populations to confirm the results. They showed that the same genetic
change in IL-7R increased the risk of MS to a very similar extent in four
different populations.
According to Gregory, as research builds upon the altered function
of IL-7R, the mechanisms involved in the development of MS will be
unlocked, which may lead to novel treatments for the disease or the
identification of targets for new therapies.
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CNS Drug News
Nuon raises funds to advance tranilast development
Nuon Therapeutics has completed a US$5 million series A financing,
capital that will support clinical studies of its orally-active lead
compound, tranilast, targeting multiple sclerosis (MS), rheumatoid
arthritis (RA) and pain.
Kissei Pharmaceutical has marketed tranilast (under the brandname
Rizaben) in Japan and Korea for bronchial asthma since 1982.
Indications for keloid and hypertrophic scar were added in 1993. In
addition, a Rizaben eye drop was launched in 1995 in these markets
and is widely used for allergic conjunctivitis. Tranilast is thought to act
in these diseases by inhibiting the release of chemical inflammatory
mediators from mast cells. Nuon's strategy is to reposition it to treat
MS, RA and pain, as well as build a portfolio of additional drugs in
autoimmune disease and pain. Nuon's founding scientists have
conducted wide-ranging preclinical testing of tranilast, with the
compound showing improvement in an animal model of MS.
The funding will enable Nuon to advance tranilast through the next
phase of clinical development, as well as support the discovery and
development of additional compounds. Initially, the funds will be used
to develop and protect the company's intellectual property, hire staff,
secure supply of drug product, undertake related licensing and open
an FDA IND application.
For details of Nuon completing a licensing, supply and collaboration
agreement with Kissei for tranilast, see Agreement News.
BioMS' RRMS trial receives positive DSMB review
The independent Data Safety Monitoring Board (DSMB) for BioMS
Medical's Phase II MINDSET-01 trial of MBP8298 in patients with
relapsing-remitting multiple sclerosis (RRMS) has completed a safety
analysis and recommended that the trial continue as per the protocol.
This was the first of several regularly-scheduled reviews by the DSMB
that will occur over the duration of the study.
MINDSET-01 is a 15-month, double-blind, placebo-controlled trial. The
objectives of the study, which is fully enrolled with approximately 215
patients at 24 sites in six countries, are to demonstrate the safety and
efficacy of MBP8298 versus placebo, as measured by relapse rate, MRI
activity and disease progression.
Product News
GW withdraws European application for Sativex in MS
spasticity
GW Pharmaceuticals has chosen to withdraw its current regulatory
application for Sativex, a cannabis-derived, oro-mucosal spray
composed primarily of tetrahydrocannabinol and cannabidiol, in
Europe, but expects to resubmit an application for approval in 2008.
This follows constructive and detailed discussions with regulatory
authorities in which they have provided a clear path to approval for
Sativex in the treatment of multiple sclerosis (MS) spasticity.
In September 2006, GW filed an application for Sativex under the
decentralised procedure in four European countries (the UK, Spain,
Denmark and the Netherlands) for the relief of MS spasticity. The
company has been able to successfully resolve all the major questions
raised by the regulators during this process except one, and at a recent
meeting with the UK assessors, it became clear that this outstanding
2nd August 2007
CNS Drug News
issue requires the generation of additional data. As European
regulatory rules do not permit the introduction of new data as part
of the current process, GW has elected to withdraw and resubmit its
application.
The regulator's outstanding clarification relates to the fact that in
a clinical trial context, the benefit obtained by "responders" can
be masked by looking at the mean improvement across the entire
studied patient population, which comprises both responders and
non-responders. The regulators therefore wish to be able to identify
Sativex responders in the first four weeks of treatment and to confirm
that the improvements gained by such responders over a further 12-
week period is significantly greater than placebo.
As part of the current regulatory process, GW performed analyses of
existing data showing that responders can be reliably identified after
four weeks and that after 12 weeks, the difference from placebo is
clinically important and highly statistically significant (p=0.015). The
regulators view this as acceptable evidence of efficacy in principle,
but consider these analyses technically to be post hoc since they were
performed at the regulator's request following completion of the trials.
They require such data to be produced as part of a prospectively-
planned analysis and hence GW will undertake an additional study to
reconfirm this result prior to resubmitting its regulatory application.
The regulators have given GW clear guidance as to the design of
the required further study, which differs from a conventional Phase
III design. The study is expected to start recruiting patients in the
next few months, with the results due in the second half of 2008.
The regulators have specified a novel "enriched design," which first
identifies responders over a four-week period and then focuses on
analysing the effect of Sativex versus placebo on those responders
over a further period of time. GW's clinical plans for the next 12
months already included a further MS spasticity trial, therefore the
regulator's specific design requirements will be incorporated into this
planned study.
There are two potential opportunities for early resubmission in Europe
next year. In the indication of MS neuropathic pain, a second pivotal
Phase III trial is expected to complete in early 2008, which could
lead to a regulatory filing in this indication at that time. Since this is a
distinct indication from MS spasticity, the outstanding issue identified
as part of this recent application would not be relevant. In the event
that GW does not submit for this indication, the second opportunity
is to resubmit for MS spasticity later in 2008, following completion of
the new study.
Elsewhere, the company anticipates receiving final regulatory approval
in Canada for the cancer pain indication in the coming weeks and its
first large-scale clinical trials in the US are scheduled to commence in
late summer. To date, GW has entered into Sativex licence agreements
with Otsuka in the US, Bayer HealthCare in the UK and Canada, and
Almirall in Europe (excluding the UK).
Agreement News
Glenmark purchases rights to CHR-1103 and CHR-1201
from Chromos
Glenmark Pharmaceuticals has completed its purchase of Chromos
Molecular Systems' two new biological entities (NBEs), CHR-1103 and
CHR-1201, which are humanised therapeutic monoclonal antibodies
(MAbs). Under the terms of the transaction, Glenmark has purchased
all rights to the two products, as well as rights to use Chromos'
2nd August 2007 ©
Espicom Business Intelligence
NEURODEGENERATIVE DISORDERS
23 - 25 October 2007
The Royal Garden Hotel
London, United Kingdom
CNS disorders: today’s science to
tomorrow’s market
CNS disorders are one of the leading causes of mortality
worldwide. According to reports, neurological disorders
affect over 1 billion people globally. The prevalence of these
disorders is rising, principally driven by a global aging
population. However there is a lack of blockbuster drugs and
targeted therapies to cater for the number of patients and
range of disorders.
NeuroDrug 2007 focuses on drug discovery and development
across the CNS sector. Our agenda focuses on novel
therapeutic targets for neurological, neurodegenerative and
psychiatric disorders. Key learning include case studies on
cutting edge drugs and therapies, lead optimisation, novel
biomarkers and imaging, latest approaches to drug delivery
and crossing the blood brain barrier.
The best mix of expert speakers from the
pharmaceutical and biotech sectors
Our senior level speakers come from world class
pharmaceutical companies, leading biotechs and unrivalled
medical research centres. Represented companies include
GlaxoSmithKline, AstraZeneca, Johnson & Johnson, Wyeth,
Eli Lilly, Boehringer Ingelheim, Schering-Plough, UCB
Pharma, Lundbeck, Pierre Fabre, Otsuka Maryland
Medicinal Laboratories, Oxford BioMedica and the
Foundation for the NIH. 90% of speakers are CxO’s,
Therapeutic Area Heads, Directors or Presidents. Advances
in CNS drug discovery and development are best achieved
through knowledge sharing and collaborations.
Eli Lilly explains why this is a must
attend event
"Neurodrug 2007 offers an excellent insight into multiple
aspects of CNS drug discovery. The meeting has topics that
relate to most CNS disorders such as new technology, drug
delivery, biomarkers and more specific focused topics such
as small molecule, viral delivery and stem cell approaches to
treat neurodegeneration. The varied approaches taken for
certain diseases should make an interesting meeting with
opportunity to discuss and network".
Dr Michael J. O'Neill, Research Advisor,
Neurodegeneration Drug Team, Eli Lilly
3 easy ways to register
Online: www.lifescienceworld.com/2007/neuro
Email: julie.phillips@terrapinn.com
Tel: +44 (0) 207 539 4336
Event code: 14/1318 / Espicom
Page 
NEURODEGENERATIVE DISORDERS
proprietary ACE System technology for cell line development for use
with respect to the two NBEs. Glenmark holds the worldwide rights
for further development, registration and commercialisation of these
products. Further terms were not disclosed.
The NBEs are part of a validated class of drugs known as selective
adhesion molecule inhibitors. CHR-1103 is a broad anti-inflammatory
agent with a novel mechanism of action that is initially being
developed to treat acute multiple sclerosis. Glenmark plans to initiate
Phase I trials in 2008 and complete this stage of development with
CHR-1103 by March 2009. CHR-1201 is an antithrombolytic humanised
MAb that Glenmark initially plans to develop to treat acute stroke; the
company plans to start Phase I development with CHR-1201 by March
2009.
Nuon and Kissei complete tranilast agreement
Nuon Therapeutics has completed a licensing, supply and
collaboration agreement for tranilast with Kissei Pharmaceutical.
The agreement will enable Nuon to advance tranilast through the
next phase of clinical development, while giving Kissei the exclusive
option right for research, development and marketing of tranilast
in Japan and Korea in the autoimmune disease field, including
multiple sclerosis (MS). The partnership will enable multiple Phase II
development programmes.
The terms of the agreement include provisions for Kissei to
supply tranilast to Nuon for clinical trials and license Nuon-related
intellectual property (IP) on the compound. The agreement also
establishes a collaborative relationship between the companies for
the development of additional portfolio products. Nuon has licensed
and developed worldwide IP for the use of tranilast to treat MS,
rheumatoid arthritis, pain and other indications.
For details of Nuon raising funds to advance tranilast's development,
see R&D Update.
Other Neurodegenerative Disorders
- R&D Update
TBZ protects brain cells in HD model
University of Texas Southwestern Medical Center researchers have
found that a drug used in some countries to treat the symptoms
of Huntington's disease (HD) prevents the death of brain cells in
mice genetically engineered to mimic the hereditary condition. The
research, which was published in the 25th July issue of the Journal
of Neuroscience (2007;27:7899-7910), sheds light on the biochemical
mechanisms involved in the disease and suggests new avenues
of study for preventing brain cell death in at-risk people before
symptoms appear.
The drug, called tetrabenazine (TBZ), is commercially distributed
as Xenazine or Nitoman and blocks the action of dopamine. TBZ
is approved for use in several countries, but not the US, to treat
uncontrollable muscle movements in HD and other neurological
conditions.
In the study, the researchers used mice that were genetically
engineered to carry the mutant human gene for HD, causing
symptoms and the death of brain cells similar to those seen in the
disease. The study focused on the striatum, which is primarily made
up of medium spiny neurons that undergo widespread death in HD.
Page  ©
Espicom Business Intelligence
CNS Drug News
The researchers conducted various co-ordination tests on both
normal and genetically-manipulated mice. Engineered mice given
a drug that increased brain dopamine levels performed worse on
these tasks, while TBZ protected against this effect. Most importantly,
TBZ appeared to significantly reduce cell loss in the striatum of the
engineered mice.
More research is needed to determine whether this protective effect
might also be present in humans and if at-risk people would benefit
from the drug. However, senior author, Dr Ilya Bezprozvanny, believes
that clinical trials would be difficult, because they require many
participants and there is no easy way to score the effectiveness of a
presymptomatic drug. Thus, his future studies in animals will look
at the effectiveness of TBZ given just after initial symptoms have
developed, a situation that simulates what would probably happen in
a human trial.
Editor's note: Cambridge Laboratories has worldwide rights to TBZ and
markets the product itself in the UK and Eire, and through marketing
partners in Europe and other global markets.
Avicena to proceed with confirmatory Phase III ALS
trial
Avicena Group has met with the FDA and plans to proceed with a
confirmatory Phase III trial of its lead drug candidate, AL-02, for the
treatment of amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease).
Two completed Phase III studies demonstrated a positive trend
towards increased survival at nine months and Avicena will be
analysing the data at the 18-month time point to confirm a longer-
term survival benefit. These data will be used to support the new
Phase III study, which is planned to commence in 2008 and will be
designed to evaluate AL-02's potential to increase survival.
First patient treated in Phase II trial of Dimebon for
HD
The first patient has been treated in Medivation's Phase II trial of
Dimebon to treat Huntington's disease (HD), plus the company has
expanded enrolment in the study by 20 per cent (to 90 patients)
in order to enhance the ability to detect differences between the
compound and placebo.
Medivation is conducting the trial in collaboration with the
Huntington Study Group (HSG). The Phase II portion will be
conducted at approximately 17 HSG sites in the US and Europe, and
is a randomised, placebo-controlled, double-blind evaluation of the
safety and preliminary efficacy of Dimebon in 90 patients with HD
after three months of dosing. The primary efficacy endpoint of the
Phase II portion is the UHDRS and Medivation expects to report study
data in the first half of 2008. According to the company, the results
from the Phase I portion of the study have allowed it to move forward
to the preliminary efficacy phase.
Dimebon is an orally-available small molecule that has been shown
to prevent the death of brain cells in preclinical models of HD and
Alzheimer's disease, making it a novel potential treatment for
these and other neurodegenerative diseases. Based on the clinical
and preclinical data generated, to date, Medivation believes that
Dimebon operates by a novel mechanism of action and may exert a
neuroprotective effect in multiple areas of the CNS. Dimebon appears
to block a new target that involves mitochondrial pores, which
are thought to play a role in the cell death that is associated with
neurodegenerative diseases and the ageing process.
2nd August 2007
CNS Drug News
Intellect reports positive safety data from Phase Ia
Oxigon trial
Intellect Neurosciences has obtained validated data and an audited
report describing the results of a Phase Ia trial of Oxigon, which
indicate no serious adverse effects in any of the subjects throughout
the dose levels.
This double-blind, randomised, placebo-controlled, single escalating-
dose study in 54 elderly healthy volunteers was conducted in
the Netherlands under Ethics Committee approval in Utrecht.
Intellect designed the trial to determine the safety, tolerability and
pharmacokinetics of Oxigon with and without food interactions.
Oxigon is a chemically-synthesised form of a small, naturally-occurring
molecule that has unique antifibrillogenic, neuroprotectant and
antioxidant properties. Oxigon can reduce the accumulation of
toxic soluble amyloid beta peptides and inhibit plaque deposition.
Simultaneously, it acts as a neuroprotectant, preventing neuronal
damage from amyloid beta-induced oxidative stress. Preclinical
studies using transgenic mouse models have provided evidence that
the compound has the potential to reduce brain amyloid burden
and improve cognition in Alzheimer's disease, while additional
studies have demonstrated its potential utility to treat indications
and conditions such as Parkinson's, Huntington's and other diseases
in which oxidative stress is believed to be a significant contributing
factor.
Intellect is the exclusive licensee of patents related to the use of
Oxigon, which are owned jointly by New York University and the
University of South Alabama. Patents have been granted in Europe,
the US and several other countries.
Product News
Neurochem receives second FDA approvable letter
for Kiacta in AA amyloidosis
Neurochem has received a second approvable letter from the FDA for
Kiacta (eprodisate), for the treatment of amyloid A (AA) amyloidosis.
In its action letter, the FDA indicated that the Phase II/III trial provided
some evidence of the effectiveness of Kiacta, which has received
orphan drug status in the US, EU and Switzerland, for the treatment
of the renal manifestations of amyloidosis, however, the Agency also
indicated that an additional efficacy trial with a target p-value of 0.05
will be necessary before it could approve the investigational product
candidate.
Furthermore, the approvable letter stated that additional submissions,
filed by Neurochem as part of its complete response to this
approvable letter, may address issues raised in this letter. The FDA
has indicated that such additional submissions could persuade it
to eliminate the requirement for an additional trial. The Agency also
asked for additional information, including further pharmacokinetic
studies, and again acknowledged that a QT clinical study should be
submitted as part of a Phase IV commitment. The company expects to
file a complete response to this approvable letter in the near future.
Rilutek patent ruled not invalid
The US District Court for the District of Delaware has ruled that Aventis
Pharmaceutical's (sanofi-aventis) Patent No. 5,527,814 related to
the use of Rilutek (riluzole) for the treatment of amyotrophic lateral
2nd August 2007 ©
Espicom Business Intelligence
NEURODEGENERATIVE DISORDERS
sclerosis (Lou Gehrig's disease), is not invalid on the grounds of
anticipation. This decision comes following a remand from the Court
of Appeals for the Federal Circuit in November 2006, in which the
Court had vacated an earlier decision of patent validity and remanded
for further findings relating to a specific validity issue of anticipation
by a prior art patent.
Impax Laboratories' ANDA for its generic version of Rilutek 50mg
tablets was approved on 29th January 2003 by the FDA, but the
product has never been sold due to an injunction entered in this
patent litigation.
Agreement News
Biogen Idec to exercise first milestone investment in
ALS collaboration with Amorfix
Amorfix Life Sciences has received notice from Biogen Idec that it will
be exercising the first milestone investment under an August 2006
research and investment agreement.
The milestone investment allows Biogen Idec to retain its exclusive
worldwide option to license Amorfix' therapeutic candidates for
amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). Biogen Idec
will subscribe for 91,445 shares of Amorfix at a price of C$1.76 per share
for gross proceeds to Amorfix of US$150,000; the shares are subject to
a four-month hold period.
The companies entered into the agreement to develop and
commercialise Amorfix' technology directed against ALS, which
includes an option for Biogen Idec to license the exclusive worldwide
rights to the technology. According to Amorfix, which has achieved
the first of three predefined milestones for its therapeutic ALS
programme with Biogen Idec, the research is focused on the role
of monoclonal antibodies (Abs) targeted to misfolded superoxide
dismutase-1 (SOD1) for the treatment of ALS.
Amorfix has demonstrated that a targeted immunotherapy approach
can diminish the motor neuron effects of ALS in animals. Its approach
is based on the premise that the misfolding and aggregation of
SOD1 is a principal agent in the death of motor neurons in all types
of ALS disease. Amorfix believes that if the misfolded SOD1 could be
specifically recognised and neutralised by Abs prior to aggregation,
the disease could be effectively treated. This approach could be
extended beyond ALS to other misfolded protein diseases, such as
Alzheimer's and Parkinson's, where misfolded proteins have been
identified.
Tikvah/Academia Sinica enter licensing agreement for
neurodegenerative disorders
Tikvah Therapeutics has entered into an exclusive licensing agreement
for a number of patent and patent applications with Academia Sinica
encompassing the diagnosis, methods of use and treatments of a
variety of neurodegenerative disorders, including, amongst others,
spinal muscular atrophy (SMA). The subject of this agreement is
technology developed at Academia Sinica.
Under the terms agreed, Tikvah will be conducting the clinical
development of agents. Tikvah will pay a licensing fee, potential
milestones and royalty payments in exchange for an exclusive licence
to pursue the commercial development of the technology for the
treatment of SMA and other neurodegenerative diseases.
Page 
CEREBROVASCULAR DISORDERS / ANXIOLYTICS/SLEEP DISORDERS
Cerebrovascular Disorders
R&D Update
SYGNIS completes Phase IIa study of AX200 in stroke
SYGNIS Pharma has successfully completed a multi-centre, double-
blind, placebo-controlled, dose-escalation, Phase IIa study of AX200
in stroke. A comprehensive analysis of the AXIS study data show that
the primary and secondary endpoints were achieved and that the
use of AX200 in stroke patients can be considered safe. Although the
focus of the study was the collection of data regarding safety and
tolerability, data on the efficacy of AX200 were also monitored. Due
to the small number of patients involved in such a safety study, a
Anxiolytics/Sleep Disorders
R&D Update
deCODE discovery points to new RLS treatment
approach
Scientists at deCODE genetics, in collaboration with colleagues from
Emory University, have discovered the first variant in the sequence of
the human genome ever linked to risk of restless legs syndrome (RLS)
and periodic limb movements (PLMs).
The SNP in the BTBD9 gene on chromosome 6 was associated in
Icelandic and US cohorts with an increased risk of RLS with PLMs of
70 to 80 per cent for those who carry one copy, compared to those
without the variant. It is believed to account for approximately 50 per
cent of cases and was shown to associate with decreased stores of iron
in the body.
The discovery, which was published in the 18th July online edition of
the NEJM (10.1056/NEJMoa072743), provides new evidence that RLS is
a genuine disease with an identifiable biological basis. deCODE plans
to analyse the BTBD9 pathway to begin a drug-discovery programme
targeting the underlying causes of disease.
The deCODE team analysed more than 300,000 SNPs in a total of
1,000 Icelandic RLS patients and controls, leading to the identification
of a single SNP on chromosome 6p21. The strongest association was
between allele A of SNP rs3923809 and the combined phenotype of
RLS with PLMs.
The rs3923809 is located within the BTBD gene, which is widely
expressed in the brain and other organs. The finding was subsequently
confirmed in a case-control cohort from the Emory Healthcare
Program in Sleep in Atlanta, GA.
The variant identified also confers risk of PLMs without RLS, with
individuals carrying two copies of the at-risk variant having two-fold
risk of PLMs compared to those that do not carry a copy of the variant.
Analysis of the impact of the variant on serum ferritin levels, a principal
indicator of iron stores in the body, showed that serum ferritin was 13
per cent lower per copy of the variant carried compared to controls.
Hence, this discovery supports an old notion that the pathogenesis of
RLS may involve iron metabolism.
Page 10 ©
Espicom Business Intelligence
CNS Drug News
significant difference between AX200- and placebo-treated patients
could not be observed in the overall consideration of the usual clinical
endpoints. However, a detailed statistical evaluation of the data
provided has suggested that certain stroke patients may benefit from
a treatment with AX200.
Besides stroke, SYGNIS is currently preclinically testing the
endogenous protein, AX200, in further neurodegenerative indications,
such as amyotrophic lateral sclerosis (Lou Gehrig's disease).
Following the positive results of the AXIS study, SYGNIS is in the
process of designing and preparing a Phase IIb trial, the aim of which
will be to demonstrate the efficacy of AX200 in stroke patients.
Severe trauma may affect children's brain function
The first study to examine brain activity patterns in severely-
traumatised children has suggested that their brains function
differently than those of healthy children, according to researchers
at the Stanford University School of Medicine and Lucile Packard
Children's Hospital.
The study, which was published in the 27th June online edition of
Depression and Anxiety (10.1002/da.20346), hints at the biological
underpinnings of post-traumatic stress disorder (PTSD), as well as
provides a valuable benchmark with which to assess the effectiveness
of potential therapies. However, it is not yet clear whether the brain
differences are caused by the interpersonal trauma experienced by
the children or if pre-existing differences make some children more
susceptible to developing PTSD after traumatic events than their more
resilient peers.
The researchers used functional MRI (fMRI) to compare brain
activation patterns in 16 children with symptoms of PTSD to the
patterns seen in 14 age- and gender-matched non-traumatised
children as they performed a simple decision-making task. It was
found that although the two groups accomplished the task equally
well, they used different parts of their brains to do so. The children
with PTSD symptoms showed less activity than their non-traumatised
peers in the left middle frontal cortex, an area known to be involved
in response inhibition, and more activity in several other areas of the
brain, including the insula.
People with PTSD often have trouble paying attention and responding
appropriately to experimental tasks, perhaps due to heightened
physiological arousal arising from their traumatic experience. As
a result, many children with PTSD symptoms are diagnosed with
attention deficit hyperactivity disorder, but it is difficult to tell whether
the two disorders are truly related, or if they simply have overlapping
symptoms; functional imaging such as fMRI may allow researchers to
solve this mystery, plus it may help doctors to devise better therapies.
According to lead author, Dr Victor Carrion, it may be possible to
redirect the brain's altered processing functions. Ideally, people
will one day be able to compare brain images from before and after
treatment to determine what does or does not work for children with
PTSD.
2nd August 2007
CNS Drug News ANXIOLYTICS/SLEEP DISORDERS

Product News Market An expanding

forecasts and market, a

BiOequivalent generiC drugs in Brazil

Sepracor submits Lunivia MAA trend analysis! growing
Sepracor has submitted an MAA for Lunivia (eszopiclone) to the EMEA population,
for review under the centralised procedure, with EU approval targeted
for the second half of 2008. Eszopiclone is known in the US as Lunesta
a regulatory
and indicated for the treatment of insomnia. regime supportive of the
The MAA contains results from 122 preclinical and 35 clinical studies,
generics sector, robust
which included more than 5,500 adult and older adult (>65 years of domestic production and
age) subjects, including patients with transient or chronic insomnia.
In addition to studies of the drug in patients with insomnia and co-
many untapped opportunities.
existing conditions, two six-month, placebo-controlled studies in Is Brazil the place for generic
primary insomnia, as well as two driving studies that Sepracor believes
will support a European labelling claim that Lunivia shows no effect
companies to be?
on next-day driving (as measured by brake reaction time) in healthy
subjects or subjects with insomnia, were included as part of the The world’s major emerging
submission. economies are attracting much
investment and interest. Brazil is not
Sepracor has also commenced enrolment in its six-month,
Pan-European study of Lunivia co-administered with Wyeth least among them, and it is easy to see
Pharmaceuticals' Effexor XR (venlafaxine) in subjects with insomnia why with a population of 189 million
and co-existing major depressive disorder. This 640-patient trial seeks and a GDP of US$978 billion in 2007.
to assess the potential benefit of Lunivia in the reduction of symptoms
of depression and in relapse prevention.
Key areas addressed:
For details of an agreement for the development and • 5-year market forecast to 2012
commercialisation of eszopiclone for the Japanese market, see
• The generics market in context
Agreement News.
• Review of the product registration
Caraco receives tentative FDA approval for generic procedure
Provigil • Pricing issues and reimbursement
• Political, legal and economic
On 18th July, the FDA granted tentative approval for Caraco
Pharmaceutical Laboratories' ANDA for modafinil tablets 100 and assessment
200mg, which is indicated to improve wakefulness in patients with • Insightful review of 20 major
OppOrtunities and Challenges fOr

excessive sleepiness associated with narcolepsy and is bioequivalent domestic and foreign players in
to Cephalon's Provigil.
the market
• Detailed product registration data
Agreement News • Who produces what?
Eisai enters partnership for Sepracor's eszopiclone

Eisai has entered into an agreement for the development and All this and more can be found in
commercialisation of Sepracor's insomnia product, eszopiclone, this new 200-page management
which is known as Lunesta in the US and Lunivia in Europe, for the
Japanese market. Under the terms agreed, Eisai will be responsible
report, published in April 2007
for completing the remaining clinical trials necessary for attaining
marketing approval from the Japanese regulatory authorities and
contingent on regulatory approval, commercialisation of the product
in Japan.
Includes A weAlth
of InformAtIon
Sepracor anticipates that the Japanese marketing application will be
submitted in 2010 or 2011. In exchange, the company is entitled to not AvAIlABle In
receive an initial milestone payment and subsequent payments upon
the accomplishment of various development, regulatory and pricing
englIsh elsewhere!
milestones, as well as royalties on product sales and compensation for
providing the product's active ingredient.

For details of Sepracor submitting an MAA for Lunivia, see Product

News.
www.espicom.com/brazilgen
2nd August 2007 ©
Espicom Business Intelligence Page 11
ANTIDEPRESSANTS / PSYCHOTIC DISORDERS
Antidepressants
R&D Update
Add-on mecamylamine treatment shows positive
effects in depression
At the Summer Meeting of the British Association for
Psychopharmacology (BAP), held from 22nd to 25th July, in Harrogate,
the UK, Targacept presented positive research findings suggesting that
an add-on treatment of mecamylamine, a broad-spectrum nicotinic
antagonist, improved symptoms of depression in patients who were
inadequate responders to first-line citalopram therapy.
The study included an open-label citalopram phase and a subsequent
double-blind, placebo-controlled phase in which the effects of
mecamylamine taken with citalopram, a treatment combination
known as Tridmac, were evaluated in patients who did not respond
adequately to citalopram alone. In the trial, the treatment combination
of mecamylamine and citalopram was generally well tolerated. Also,
patients showed greater improvement on symptoms of depression
and irritability when augmented with mecamylamine, as compared
to placebo. Patients for the trial were recruited from nine out-
patient facilities, one in the US and eight in India. Of the 472 subjects
screened, 450 entered the trial and 192 were randomised to double-
blind medication. Mecamylamine represents a new class of promising
antidepressant medications that target the brain's neuronal nicotinic
receptors (NNRs). Targacept's depression programme also includes
TC-5214, one of the enantiomers of mecamylamine hydrochloride
and a preclinical product candidate as an augmentation therapy, and
TC-2216, a product candidate as a monotherapy for depression and
anxiety disorders that is currently in an ongoing Phase I trial.
Psychotic Disorders
R&D Update
BL-1020 shows antipsychotic efficacy; enters Phase II
trial in schizophrenia
BioLineRx has successfully completed a study determining the clinical
binding properties of BL-1020 to dopamine receptors in the brain. The
study has shown that BL-1020, an orally-available, GABA-enhanced
antipsychotic clinical candidate for the treatment of schizophrenia,
blocks dopamine receptors in the human brain, providing direct
evidence of antipsychotic efficacy. The study further supports the
safety of BL-1020, as well as provides evidence that 32mg will be
clinically efficacious and that the compound can be given once daily.
The study's primary objective was to investigate the receptor
occupancy of BL-1020 in the human brain, however additional safety,
tolerability and pharmacokinetic data were also generated. The study
was conducted in Uppsala, Sweden, and designed as a single-centre,
randomised, open-label evaluation performed on three cohorts,
each with four healthy male subjects (aged 21 to 35 years) receiving
a single dose of BL-1020 16, 24 or 32mg. Receptor occupancy was
assessed using PET scans at 1.5, six or 24 hours post-dosing. The
PET data demonstrated a dose-dependent increase in dopamine
Page 12 ©
Espicom Business Intelligence
CNS Drug News
For details of further NNR research and a collaboration by Targacept,
see Neurodegenerative Disorders, Alzheimer's Disease - R&D Update;
General Development News, R&D Update; and General Development
News, Agreement News.
Product News
Abilify sNDA granted priority review by FDA
The FDA has accepted for filing and granted a priority review of the
sNDA for Bristol-Myers Squibb/Otsuka Pharmaceutical's atypical
antipsychotic, Abilify (aripiprazole), for the treatment of adults with
major depressive disorder (MDD) as adjunctive to antidepressant
therapy (ADT). The application is based on data from two six-week,
double-blind, randomised, placebo-controlled, multi-centre trials
(n=743) evaluating the use of adjunctive Abilify in adult patients with
a primary diagnosis of MDD who had an inadequate response to
monotherapy with one or more ADTs.
Biovail receives non-approval letter from FDA for
BVF-033
Biovail has received a non-approval letter from the FDA for its NDA
for BVF-033, a novel, once-daily salt formulation of bupropion for the
treatment of depression. The main issue raised by the Agency in its
letter related to the design of the pharmacokinetic studies required to
support the NDA.
Biovail believes that the studies were appropriate, but is evaluating
the issue and will meet with the FDA as soon as possible to discuss the
necessary steps to resolve this matter.
occupancy that supports the 32mg dose as being able to achieve
clinically-efficacious dopamine blockade. The efficacy of BL-1020 was
also demonstrated by measuring the elevation in prolactin levels, an
accepted marker for dopamine activity. There was a dose-dependent
change in prolactin level at four hours post-dosing, further validating
earlier Phase I results. Safety and tolerability data show that there have
been no significant changes in ECG, vital signs or physical examination,
clinical chemistry or haematology values.
In addition...
BioLineRx has initiated a Phase II trial to determine the maximal
tolerated dose of BL-1020 in 60 patients with schizophrenia or schizo-
affective disorder. This open-label, multi-centre, six-week, sequential
cohort study is expected to be conducted at five centres in Israel
and 12 centres in Romania. The dose ranges are based on results in
previous studies performed on healthy volunteers.
BL-1020 is being developed by BioLineRx under a worldwide exclusive
licence from Ramot at Tel Aviv University and Bar-Ilan Research &
Development, the technology transfer arms of Tel Aviv University
and Bar-Ilan University, respectively. Data from preclinical and Phase
I studies demonstrated that the compound may retain the efficacy
of currently-available typical and atypical antipsychotic drugs, while
2nd August 2007
CNS Drug News PSYCHOTIC DISORDERS

achieving a higher safety profile, as evidenced by a lack of metabolic

or extrapyramidal side effects. Based on its previous results, the
Many claim the BRIC countries present

The MarkeT for PharMaceuTicals in Brazil, russia, india & china 2007
company believes that BL-1020 has the potential to be clinically the most exciting opportunity for
efficacious, with minimal therapy-limiting side effects, and expects pharmaceutical manufacturers. Maybe,
Phase IIa trial results during the fourth quarter of 2007. but separating the fact from the fiction
is essential in making sound business
Drug may help people with OCD; to be tested on judgements.
smokers These leading emerging and rapidly-growing
economies represented a total market of 2.7
Researchers at the University of Minnesota have found that a drug billion people and a combined GDP of US$5.2
originally developed to fight tuberculosis may help people with trillion in 2006. But where do commercial
obsessive-compulsive disorder (OCD) to make more progress opportunities exist for pharmaceutical companies
in therapy sessions. The drug, D-cycloserine, is believed to help now?
accelerate ''extinction learning'' and the team now wants to see if it
could have a similar effect on people who want to quit smoking. COMPARATIVE OVERVIEW
This extensive section compares and contrasts
In this research project, which was led by Dr Matt Kushner and the economic, health and pharmaceutical
published in the 22nd June online edition of Biological Psychiatry
operating environment in the 4 markets.
(10.1016/j.biopsych.2006.12.020), investigators separated patients with

B
OCD into two groups. One group received the drug and the other COUNTRY ANALYSIS
received placebo, several hours before psychotherapy.
• Key National Indicators
It was found that those who took D-cycloserine made progress in • Healthcare System
therapy more quickly and were less likely to quit therapy compared • The Pharmaceutical
with the placebo group. The research subjects who took the drug Market
reported feeling less distress or anxiety due to their obsessions or • Accessing the Pharma

R
compulsions. The drug seemed to be most effective in the first few Market
therapy sessions. Over time, people in the placebo group could • Contact Details
catch up in terms of therapy goals, but more study participants in the
placebo group dropped out of therapy. The drop-out rate decreased QUARTERLY UPDATE
dramatically; typically, approximately 20 to 30 per cent of people with REPORTS INCLUDED!
OCD drop out of therapy, but only 7 per cent of people who took D-
cycloserine did so. Buyers of this report will
receive, for each market,

I
According to Kushner, the drug must be taken in conjunction with 4 quarterly reports
therapy to be effective. His team is now studying how it will effect covering:
smokers who want to quit and is seeking participants. This project will • Current market size
investigate whether or not a similar extinction learning effect will be • Unique 5-Year market
seen in people who smoke. projections to 2011
• Market outlook &
Study participants will be given nicotine-extracted cigarettes to structure
smoke and similar to the previous study, one group will receive the • Comment & rating

C
drug and another placebo, prior to therapy sessions. Participants will • Imports & export data
attend sessions once weekly for four weeks and be asked to smoke
• Market developments,
only the nicotine-extracted cigarettes in between the sessions.
covering recent
Children show sustained improvement after ADHD and impending
treatment developments with
respect to key issues
It has been reported that most children treated in a variety of ways such as regulation,
for attention deficit hyperactivity disorder (ADHD) showed sustained health facilities, and funding
improvement after three years in a major follow-up study funded
Copies of The Market for Pharmaceuticals in
by the National Institute of Mental Health, yet increased risk for
behavioural problems, including delinquency and substance use, Brazil, Russia, India & China 2007
remained higher than normal. are available for £1295 / $2655 / €2330 from
Espicom in either print or pdf format. For
The study followed-up children who had participated in the ordering details please see the back page of this
Multimodal Treatment Study of Children with Attention Deficit issue.
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years after 14 months of controlled treatment ended. However, Dr
Peter Jensen of Columbia University and colleagues emphasised that
it would be incorrect to conclude from these results that treatment
www.espicom.com/bricp

2nd August 2007 ©

Espicom Business Intelligence Page 13
PSYCHOTIC DISORDERS CNS Drug News

M onoclonal
makes no difference or is not worth pursuing. Their report is among
four on the outcome of the MTA study published in the August issue
of the Journal of the American Academy of Child and Adolescent

a ntibodies :
what the future ANTICANCER PRODUCTS
holds • Abegrin
MedImmune
• ACA 125
After years of anticipation Cell Control Biomedical
and encouraging responses • adecatumumab
Micromet/Merck KGaA
to pathfinder products, • Antibody 3F8
monoclonal antibodies are MSKCC
now set to realise their true • BB-10901
clinical and commercial ImmunoGen
potential. But what are the •Virexx BrevaRex
prospects for the products • catumaxomab
that will lead the market? Fresius Biotech/TRION Pharma
• CNT0328
Centocor
HUGE POTENTIAL • Cotara
While large pharma companies Peregrine Pharma
predictably take aim at the largest • daclizumab
treatable populations (breast cancer, PDL BioPharma/Roche
colorectal disease, NHL, leukaemia), • epratuzumab
Immunomedics
there is an abundance of niches
• ertumaxomab
for monoclonal antibody therapy
Fresius Biotech/TRION Pharma
applications and a staggering • galiximab
number of potential disease targets. Biogen Idec
Smaller developer companies
• HA20/IMMV-106
are likely to become more visible Immunomedics
as their products move closer to • HuMax-EGFr
regulatory approval. Genmab
• ipilimumab
Bristol-Myers Squibb
That is why this new management • KW-2871
report, published in April 2007 is Kyowa Pharmaceutical
essential for everyone working in • matuzumab
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30 leading compounds originating • MDX-060
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KEY EVALUATION FOR EACH • Rencarex
PRODUCT Wilex Centocor
It is vital that new compounds can • SGN-30
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Pfizer/Amgen
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• Management/clinical expertise • belimumab
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Psychiatry (2007;46:989-1002). According to Jensen, the results suggest
that medication can make a long-term difference for some children if
it is continued with optimal intensity and not started or added too late
in a child's clinical course.
Progressive grey matter loss discovered in BPD
Researchers at the University of Edinburgh have found that people
with bipolar disorder (BPD) suffer from an accelerated shrinking of
their brain. The study shows for the first time that BPD is associated
with a reduction in brain tissue and proves that the changes get
progressively worse with each relapse.
Furthermore, the findings, which were published in the 9th July online
edition of Biological Psychiatry (10.1016/j.biopsych.2007.03.005), show
that the loss of grey matter tissue is concentrated in areas of the brain
that control memory, face recognition and co-ordination, namely the
hippocampus, fusiform gyrus and cerebellum, respectively.
According to lead researcher, Dr Andrew McIntosh, this discovery
has implications for the way the disease is researched and may also
impact the way it is treated. The amount of brain tissue that is lost is
greater in people with multiple episodes of illness and is associated
with a decline in some areas of mental ability. However, McIntosh
believes another possibility is that the brain changes are caused by
stress or genetic factors, which tend to lead both to more frequent
illness episodes and to greater brain loss, thus further research will be
required.
Product News
EMEA recommends authorisation of first generic
medicine for human use
The EMEA has adopted a positive opinion recommending, for the
first time, the granting of a marketing authorisation for a generic of a
centrally-authorised medicine for human use. The recommendation
was made by the Agency's CHMP at its July meeting.
This first positive opinion is for Zalasta (olanzapine), from Krka, which is
intended for the treatment of schizophrenia and moderate-to-severe
manic episode. The reference product for Zalasta is Eli Lilly's Zyprexa
(olanzapine), which has been authorised in the EU since 1996. The
CHMP recommendation will now be forwarded to the EC for adoption
of a decision.
Shire's Vyvanse available in US pharmacies
Shire's Vyvanse (lisdexamfetamine dimesylate), a new once-daily
medication approved to treat the symptoms of attention deficit
hyperactivity disorder (ADHD), is now available in US pharmacies
nationwide. The FDA approved Vyvanse on 23rd February and the
product is now available in retail pharmacies in 30, 50 and 70mg
dosage strengths.
Vyvanse works with the patient's natural metabolism to deliver active
medication and significantly improves core ADHD symptoms of
inattention and behaviour. In a randomised, double-blind, placebo-
controlled, Phase III study, all three doses of the drug demonstrated
significant improvements in ADHD Rating Scale-IV scores compared

Page 14 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News
with placebo (p<0.0001) after four weeks of once-daily treatment. The
effects were maintained throughout the day based on parent ratings
reported at approximately 10am, 2pm and 6pm using the Connors'
Analgesics/Anaesthetics
R&D Update
Study may accelerate research into next generation of
painkillers
Scientists studying amoeboid organisms commonly known as slime
moulds have helped to unravel the structure of a key molecule that
controls pain in humans. It is thought that the findings, published in
the 12th July issue of Nature (2007;448:200-203), could rapidly advance
research into the next generation of painkillers for the relief of chronic
conditions, such as migraine and backache.
Chronic pain has no apparent physiological benefit, often being
referred to as the ''disease of pain.'' Complete and lasting relief of
chronic pain is rare and often, the clinical goal is pain management
through one or more medications. But now, researchers at the
University of Manchester have examined the microscopic amoeboid
organisms in a bid to gain greater insight into pain molecules known
as P2X receptors.
In humans, P2X receptors look identical to one another, therefore
scientists have had difficulty understanding how they function. The
researchers discovered that there was only a 10 per cent similarity
between human P2X and the slime mould equivalent, and were
therefore able to deduce from evolutionary theory that it was these
similar parts of the molecule that probably regulate pain in humans.
This is thought to be a big step forward in understanding how the
molecule works and should make it possible to develop drugs that
block the receptors' actions. Inhibiting P2X as a potential pain-relief
therapy could revolutionise the way that chronic pain conditions are
managed.
Durect reports positive Phase IIb Posidur data
Durect has reported positive results from a 122-patient, Phase IIb trial
of Posidur (SABER-bupivacaine) for the treatment of postoperative
pain in patients undergoing inguinal hernia repair, where the long-
acting local anaesthetic demonstrated statistically significant
reductions in pain and total consumption of supplemental opioid
analgesic medications versus placebo.
The multi-centre, double-blind, placebo-controlled study was
conducted in Australia and New Zealand, and designed to evaluate the
tolerability, activity, dose response and pharmacokinetics of Posidur
in patients undergoing open inguinal hernia repair. Participants
were randomised into three treatment groups: Posidur 2.5mL (n=43),
Posidur 5mL (n=47) and placebo (n=32).
In relation to the co-primary endpoint of pain reduction, as measured
by Mean Pain Intensity on Movement area under the curve (AUC)
one to 72 hours post-surgery, the patient group treated with Posidur
5mL reported 31 per cent less pain versus placebo (p=0.0033),
plus a 35 per cent reduction of pain as measured by Mean Pain
Intensity on Movement AUC for the period one to 48 hours post-
surgery, a secondary endpoint measure, was reported between the
2nd August 2007 ©
Espicom Business Intelligence
ANALGESICS/ANAESTHETICS
Parent Rating Scale. The most common side effects reported in this
study were decreased appetite, difficulty falling asleep, stomach ache
and irritability.
Posidur 5mL treatment group versus placebo (p=0.0007). A total
of 53 per cent of the study patients in the Posidur 5mL group took
supplemental opioid analgesic medications versus 72 per cent of the
placebo patients (p=0.0909). During the periods of one to 24 hours,
24 to 48 hours and 48 to 72 hours after surgery, placebo patients
consumed approximately 3.5- (p=0.0009), 2.9- (p=0.0190) and 3.6-
times (p=0.0172) more supplemental opioid analgesic medications,
respectively, than the Posidur 5mL treatment group. In addition, the
median time to first use of supplemental opioid analgesic medication
after surgery for the placebo patients was 2.7 hours versus >72 hours
for the Posidur 5mL treatment group (p=0.0197).
The patient groups treated with Posidur showed comparable safety
profiles to those treated with placebo and the drug administration
appeared to be well tolerated. Additionally, the side effects commonly
observed with opioid medication use were less frequent in the Posidur
treatment groups compared to placebo.
Durect has scheduled an end-of-Phase II meeting with the FDA in
preparation for the Phase III programme, for which it intends to select
Posidur 5mL, as this dose showed statistically significant activity
relative to placebo, whereas Posidur 2.5mL showed a positive trend
relative to placebo on certain parameters, but the results were not
statistically significant.
The decision for advancing Posidur into Phase III trials was based
on this study and the successful results trigger an US$8 million
milestone payment from Nycomed to Durect under the parties'
collaborative agreement. Durect has licensed Nycomed the exclusive
commercialisation rights to Posidur in the EU and select other
countries, plus will manufacture and supply the product to Nycomed.
The company may earn additional milestone payments of up to
US$180 million, due upon the achievement of additional defined
development, regulatory and sales milestones, in addition to blended
royalties.
Durect has also been conducting smaller exploratory Phase II studies
in hernia, shoulder arthroscopy and appendectomy surgeries to
evaluate different application techniques, clinical design and conduct,
as well as other investigational factors. In all of the exploratory studies,
patient groups treated with Posidur showed comparable safety
profiles as the placebo groups and the drug administration appeared
well tolerated. Some treatment groups from the hernia and shoulder
exploratory studies utilising Posidur have shown positive activity as
measured by a reduction of pain or the consumption of supplemental
opioid analgesic medication versus placebo, while other treatment
groups have not.
Newron reveals additional analyses of ralfinamide
Phase II study
Newron Pharmaceuticals has reported further results from the first
placebo-controlled, randomised treatment trial of ralfinamide in
patients with various types of neuropathic pain, including diabetic
neuropathy. Previously-announced results indicated the statistically
significant superiority (p=0.019; 95% CI -14.9, -1.4) of ralfinamide
compared with placebo on the patient-rated Visual Analogue Scale
Page 15
ANALGESICS/ANAESTHETICS
(VAS), while showing good tolerability at the doses tested (see CNS
165). Additional analyses have revealed that ralfinamide treatment
is associated with multiple statistically significant differences and
clinically-relevant benefit over placebo, as judged by:
• responder analysis using multiple definitions of the magnitude of
pain relief, as judged on the VAS (overall p<0.05);
• significant improvement in the mean ratings of the patient-rated
Daily Pain Diary (p=0.003; 95% CI -1.5, -0.3);
• significant improvement in the quality of sleep, as judged by the
patient (p=0.002; 95% CI -1.5, -0.4); and
• significant improvement in daily activities (p=0.033; 95% CI -1.4,
-0.1).
Meda agrees to acquire MedPointe
Meda AB has agreed to acquire MedPointe for US$520 million in cash
and 17.5 million newly-issued Meda shares. With approximately 710
employees and headquartered in Somerset, NJ, MedPointe is focused
on two of Meda's priority areas, pain and allergy/respiratory.
With the acquisition, Meda will have full marketing coverage in both
the US and Europe, with revenues approaching US$1.4 billion, and
the acquisition is expected to be accretive to Meda's EPS, at the latest,
during 2009.
Akela completes enrolment in Phase IIb trial of
Fentanyl TAIFUN
Akela Pharma (formerly LAB International) has completed patient
enrolment in its Phase IIb trial of Fentanyl TAIFUN, a fast-acting
fentanyl formulation that is delivered using the company's TAIFUN dry
powder inhaler platform.
This is a multi-centre, multi-national trial in cancer patients with severe
persistent pain on maintenance opioid therapy. The first part of the
trial is a single-arm, open-label dose titration to evaluate the effective
individual dose for significant pain relief with Fentanyl TAIFUN in the
treatment of breakthrough cancer pain.
The second part includes 28 responders from the open-label arm who
are randomised to receive the titrated doses or placebo. It is expected
that safety and efficacy data from this double-blind, placebo-
controlled extension arm will be available by early September.
Product News
Ortho-McNeil/Par settle Ultracet patent litigation
Ortho-McNeil Pharmaceutical (Johnson & Johnson) has settled patent
litigation against the generic drug manufacturer, Par Pharmaceutical
Companies, and its subsidiaries, Par Pharmaceutical and Kali
Laboratories, regarding their infringement of the patent for Ultracet
(tramadol+acetaminophen). Par received FDA approval and began
marketing its generic version of the product, which is indicated for the
short-term management of acute pain, in April 2005.
As part of the settlement, Par/Kali acknowledged that the re-issue
patent for Ultracet is valid and enforceable, and that they infringed it
by selling generic versions of the product on the US market. Par/Kali
will pay to Ortho-McNeil a lump sum for past damages and will have
a royalty-bearing licence until their product's agreed-upon exit from
the market on 15th November 2007.
Page 16 ©
Espicom Business Intelligence
CNS Drug News
Organon's MAA for sugammadex accepted for review
Organon's (Akzo Nobel) MAA for sugammadex has been accepted
for review by the EMEA. This novel selective relaxant-binding agent
is specifically designed to reverse the effects of the muscle relaxant,
rocuronium bromide (Esmeron/Zemuron), used as part of general
anaesthesia during surgical procedures.
The MAA is based on safety and efficacy data from over 1,700 patients,
including data from ten global Phase III trials. The results of four of
these studies were presented at the 14th Annual Euroanaesthesia
2007 Congress in June (see CNS 164).
Sugammadex works by encapsulating the muscle relaxant molecule
and forming a tight complex. The encapsulation of the muscle relaxant
by sugammadex removes the drug from its site of action and renders
it inactive. In clinical trials conducted, to date, sugammadex has
generally demonstrated the ability to reverse shallow and profound
depths of rocuronium-induced neuromuscular blockade within three
minutes, thereby enabling control of the onset and offset of skeletal
muscle relaxation through the use of both drugs. Sugammadex has
also demonstrated the ability to reverse the effects of vecuronium-
induced (Norcuron) neuromuscular blockade. Sugammadex' global
Phase III development programme, consisting of five US and five
European trials, completed recruitment in late 2006. The anticipated
submissions for the US and Japan are proceeding in line with the
previously-disclosed timelines.
RxElite launches generic sevoflurane in the US
RxElite Holdings (Southridge Technology) has launched Sojourn
(sevoflurane), a generic inhalation anaesthetic, in the US. The company
is Minrad International's exclusive commercial partner for the product
in this market, where it received FDA approval on 2nd May. RxElite
currently markets three anaesthetic gases in the partnership with
Minrad: sevoflurane, isoflurane and enflurane. RxElite is the third
entrant into the US sevoflurane market, following Abbott (with Ultane)
and Baxter.
US PTO allows Opana ER-related patent application
The US PTO has indicated that Penwest Pharmaceuticals' patent
application claiming the sustained-release formulation of
oxymorphone related to Opana ER (oxymorphone) extended-release
tablets CII has been allowed. Penwest received a final rejection from
the PTO for this application on 15th March, however in response to the
rejection, the company amended the claims and the PTO examiner
found these allowable.
Opana ER, which is marketed by Endo Pharmaceuticals, uses Penwest's
TIMERx technology and is indicated for the treatment of moderate-to-
severe pain in patients requiring continuous, around-the-clock opioid
treatment for an extended period of time. The patent, once issued, will
be scheduled to expire in 2022 and Penwest expects that Endo will list
this patent at the earliest opportunity in the FDA's Orange Book.
Agreement News
Hydra signs global TRPV3 collaboration with Pfizer
Hydra Biosciences has signed a collaboration agreement with Pfizer
Global Research & Development that will be focused on TRPV3
antagonist product candidates for pain. The transient receptor
2nd August 2007
CNS Drug News
potential (TRP) channel family comprises a novel group of non-
selective cation channels that are distinct from classical voltage-
gated ion channels. Under the terms agreed, Hydra will receive up-
front and success-based development milestone payments totalling
US$195 million for the first developed product launched, with upside
potential for additional approved indications. Furthermore, there
are opportunities for the development of additional products. Pfizer
will fund all research and development under the agreement, plus
receive exclusive access to Hydra's current TRPV3 patents, as well
as an exclusive licence to commercialise any compound from the
collaboration. Once the products are on the market, Pfizer will pay
worldwide royalties to Hydra.
Tikvah enters licensing agreement with Apkarian
Tikvah Therapeutics has entered into an exclusive licensing agreement
with Apkarian Technologies for patents and patent applications
involving certain agonists of specific sites of the NMDA receptor. These
Therapies to Treat Substance Dependence
R&D Update
Nabi creates pharmaceuticals business unit
Nabi Biopharmaceuticals has created the second of its two
planned strategic business units, Nabi Pharmaceuticals, which will
be responsible for the NicVAX (nicotine conjugate vaccine) and
StaphVAX (Staphylococcus aureus polysaccharide conjugate vaccine)
development programmes, as well as the continuing milestone-
related development obligations following the sale of PhosLo (calcium
acetate).
The company announced in June that it had created the Nabi Biologics
units, as well as a Corporate Shared Services group to support these
business units.
In connection with the reorganisation required to support the
business strategy of this latest unit, the company eliminated 33
positions in its Rockville, MD, research and development facility. This
reduction of approximately 5 per cent of the company's total current
workforce is expected to yield approximately US$3.3 million in savings
on an annualised basis.
Anti-Epileptics
R&D Update
Icagen files IND for novel epilepsy compound
Icagen has filed an IND application with the FDA for ICA-105665, a
novel small-molecule compound for the treatment of epilepsy.
ICA-105665 is an activator of subtypes of KCNQ ion channels, which
are attractive targets for the treatment of epilepsy based on their
function and genetic linkage to a seizure disorder. In preclinical
studies, ICA-105665 was active in animal models predictive of
2nd August 2007 ©
Espicom Business Intelligence
THERAPIES TO TREAT SUBSTANCE DEPENDENCE / ANTI-EPILEPTICS
newly-acquired rights provide Tikvah with claims encompassing the
chronic treatment of pain and pain-related indications with glycine
receptor agonists as monotherapy or in combination with certain
other agents.
The subject of this agreement is technology developed by researchers
at Northwestern University in the area of pain and perception. This
work has suggested that treatment with certain classes of glycine
receptor agonists, alone or in combination with other agents, can
be used to treat chronic pain, as well as modify the structural brain
changes that occur under conditions of chronic pain.
The studies of various brain processes in humans and animals
using non-invasive brain imaging techniques, coupled with brain
electrophysiology and knowledge of neural networks, afford a
differentiated approach to understanding the perception of touch
and pain.
Editor's note: NicVAX is Nabi's innovative and proprietary
investigational vaccine that is being developed to treat nicotine
addiction and prevent smoking relapse.
Drug may help people with OCD; to be tested on
smokers
For details, see Psychotic Disorders, R&D Update.
Product News
UK's NICE issues guidance on Champix for smoking
cessation
The UK's National Institute for Health and Clinical Excellence (NICE)
has issued guidance recommending Pfizer's Champix (varenicline) as
an effective treatment for helping smokers to quit. The drug, within
its licensed indications, is recommended as an option for smokers
who have expressed a desire to quit smoking, but should normally be
prescribed only as part of a programme of behavioural support. These
recommendations are part of a suite of guidance being produced by
NICE on the most effective methods of tackling smoking and what
works to help people quit.
efficacy for the treatment of partial seizures, generalised seizures and
treatment-resistant seizures. In addition, ICA-105665 has also been
shown to have activity in models of neuropathic and inflammatory
pain.
ICA-105665 will be administered orally and is intended to be
developed as a chronic therapy for patients with epilepsy.
Provided that the IND is accepted, Icagen plans to initiate a Phase
I trial during the third quarter of 2007; this will be a double-blind,
placebo-controlled study conducted in healthy male volunteers
to assess the safety, tolerability and pharmacokinetics of the
compound.
Page 17
EATING DISORDERS CNS Drug News

Eating Disorders
was shown to reduce the size of adipocytes, reduce body fat with no
R&D Update reduction of lean mass and improve glucose tolerance via inhibition of
a unique combination of signalling pathways in this model. MSI-1436 is
Preclinical data confirm trodusquemine's potential currently being evaluated in obese, but otherwise healthy volunteers
for obesity for a Phase I safety and pharmacokinetics study.

At the Center for Business Intelligence's 3rd Annual Obesity Drug Orexigen reports positive Phase IIb data with Empatic
Development Summit, held from 26th to 27th July, in Arlington, for obesity
VA, Genaera presented new data from preclinical studies with
trodusquemine (MSI-1436) for the treatment of obesity and Type II Orexigen Therapeutics has reported positive top-line results at
diabetes. the 24-week primary endpoint of its Phase IIb trial of Empatic
(bupropion+zonisamide; formerly Excalia), one of the company's two
The preclinical data demonstrated that MSI-1436 is a potent, highly- obesity drug candidates. The trial demonstrated, across each of the six
selective and reversible inhibitor of protein tyrosine phosphatase- Empatic treatment arms, statistically significant weight loss compared
1B (PTP-1B), an enzyme central to the function of both the leptin and to placebo (p<0.001).
insulin pathways. The mechanism of this inhibition, as indicated by in
vitro kinetics, is through binding to a site different from the catalytic The randomised, double-blind, placebo-controlled trial was
site of PTP-1B. The in vitro kinetics demonstrate that MSI-1436 is an conducted with the company's novel sustained-release (SR)
allosteric, non-competitive inhibitor of PTP-1B. Data also indicated formulation of zonisamide paired with bupropion SR, and evaluated
that MSI-1436 crosses the blood-brain barrier and is both centrally and various ratios of bupropion and zonisamide in 620 patients. At the
peripherally active. These dual locations of MSI-1436 action make the highest dose tested, patients experienced 8.6 per cent weight loss
drug a promising therapeutic candidate for both obesity and Type II from baseline, compared to 1.1 per cent weight loss for placebo in
diabetes. the intent-to-treat group, and 10.3 per cent weight loss from baseline,
compared to 1.2 per cent weight loss for placebo in the completer
As previously disclosed, preclinical studies have also demonstrated
group. In addition, the trajectory of weight loss for all treatment arms
that MSI-1436 suppresses appetite and causes differential weight
appeared to continue downward through 24 weeks.
loss in a mouse model of diet-induced obesity. In addition, MSI-1436
Results of the trial indicate that Empatic is safe and generally well
The authoritative online tolerated. The pooled discontinuation rate for adverse events
business resource for (AEs) across the six Empatic dosages was 14 per cent, which was
everyone involved in meaningfully lower than the rate in the company's previous trial
employing an older immediate-release form of zonisamide (37 per
this high growth area, cent). The pooled discontinuation rate due to AEs across the six
providing: Empatic dosage groups was not statistically different than the rate
• Company Analysis seen with placebo. AEs were consistent with the existing package
labels for the two constituents and most commonly included
Regularly updated and detailed analysis of 135 headache, nausea, insomnia, anxiety or dry mouth.
leading companies’ strategy, research, products
and agreements Empatic employs a proprietary formulation of the CNS molecules,
bupropion and zonisamide, which have been independently
• R&D and Product Developments approved by the FDA in other indications. Orexigen developed its
R&D and product developments in all major own proprietary SR version of zonisamide to improve drug tolerability.
Bupropion and zonisamide each target reciprocal pathways in
cancer areas. the hypothalamus that separately mediate appetite and energy
• Market Statistics expenditure. The unique combination of these molecules is designed
to provide more clinically-meaningful weight loss for patients by both
Demography, disease initiating weight loss and sustaining it over a longer period of time.
incidence and cause of
death for 20 markets. Orexigen's approach is designed to achieve and sustain weight
loss by enhancing satiety, diminishing appetite, improving energy
• Latest News expenditure and counteracting the body's efforts to compensate for
Track over 2,000 weight loss. According to the company, if the magnitude of weight loss
evident in this trial continues to be seen, Empatic may be particularly
companies and
useful in severely obese individuals.
organisations involved
with cancer drugs. Additional safety and efficacy data will be reported following the
completion of an ongoing 24-week trial extension. Primary trial results
For full details about this report’s content, pricing and availability go to: are to be presented at the Annual Scientific Meeting of the North

www.espicom.com/cio American Association for the Study of Obesity, to be held from 20th to
24th October, in New Orleans, LA.

Page 18 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News DRUGS USED IN NAUSEA & VERTIGO / GENERAL DEVELOPMENT NEWS
Product News
CHMP recommends upgraded warnings for Acomplia
Following an assessment of the information on psychiatric adverse
events associated with sanofi-aventis' first-in-class CB1 blocker,
Acomplia (rimonabant), the EMEA's CHMP has recommended
the addition of a contraindication in patients with ongoing major
depression or who are being treated with antidepressants, because
of the risk of psychiatric side effects. Finalising its assessment of the
available data at its 16th to 19th July meeting, the CHMP did, however,
conclude that except in these patients, the benefits of Acomplia
continue to outweigh its risks.
Acomplia has been authorised in the EU since June 2006 and is
marketed in 13 European countries as an adjunct to diet and exercise
for the treatment of obese or overweight adult patients. Psychiatric
side effects, in particular depression, were identified as the main safety
issue at the time of approval and reflected in the medicine's product
Drugs used in Nausea & Vertigo
Agreement News
Shanghai Ethypharm signs ondansetron licence
agreement with Beijing Med-Pharm
Shanghai Ethypharm Pharmaceutical (Ethypharm) has signed an
exclusive licence agreement under which Beijing Med-Pharm will
market and distribute ondansetron Flashtab (4 and 8mg) in China once
the drug is approved in this market. Under the terms agreed, Shanghai
General Development News
R&D Update
Study further links addiction and memory
People's experiences can trigger long-term changes in the strength
of connections between nerve cells in the brain and these persistent
changes are how the brain encodes information as memory. Now,
Johns Hopkins researchers have discovered a new biochemical
mechanism for memory storage, one that may have a connection with
addictive behaviour.
Previously, the long-term changes in connection were thought to
only involve a fast form of electrical signalling in the brain, however
neuroscience professor, Dr David Linden, and his colleagues have
shown that another, much slower form of electrical signalling
lasting approximately a second, can also be persistently changed by
experience.
The researchers, whose work was published in the 19th July issue of
Neuron (2007;55:277-287), simulated natural brain activity by applying
short electrical jolts to slices of rat brain and measuring the current
flowing across the cells. After repeated jolting, the strength of the
slow nerve signals had dramatically decreased and remained at a low
2nd August 2007 ©
Espicom Business Intelligence
information. The CHMP has now recommended upgrading this
warning, suggesting that treatment with Acomplia should be stopped
if a patient develops depression, as well as the inclusion of additional
information on the psychiatric safety of the drug.
Acomplia's labelling has been updated based on data reflecting a year
of post-marketing experience, mainly from Germany, France and the
UK, as well as the results of five additional clinical trials completed
since the original dossier was approved.
Editor's note: earlier in July, sanofi-aventis decided to withdraw the
NDA for rimonabant in the US, where it is branded Zimulti, following
a decision by the FDA's Endocrinologic and Metabolic Drugs Advisory
Committee to not recommend the product's approval. Additionally, in
February 2006, the company received a non-approvable letter from
the FDA's Division of Metabolism and Endocrinology Products for
smoking cessation and in May that year, the CHMP adopted a negative
opinion for Acomplia for this indication. This most recent decision
for rimonabant in obesity is unlikely to improve its chances as an
approved smoking cessation product.
Ethypharm will pursue registration of ondansetron Flashtab in China, a
process that is expected to be completed in 2009. Beijing Med-Pharm
will then be responsible for sales, marketing, distribution and supply.
Ondansetron is a member of the 5-HT3 antagonist class of anti-emetics
and marketed under the tradename, Zofran, by GlaxoSmithKline.
The drug is indicated to reduce nausea and vomiting (N&V) induced
by cytotoxic chemotherapy and radiotherapy, as well as prevent
postoperative N&V. Ethypharm manufactures the product using its
proprietary Flashtab orally-disintegrating tablet technology.
intensity for 30 minutes after electrical jolts ceased. These slow signals
are produced by a nerve cell receptor called mGluR1, which has been
associated with addiction and epilepsy. Both of these conditions also
involve long-term changes in the function of nerve connections,
therefore in addition to furthering the basic understanding of
memory storage, Linden believes the team's work suggests that drugs
designed to alter mGluR1 are promising candidates for the treatment
of addiction, epilepsy and diseases of memory.
Targacept/Abbott initiate Phase I trials of NNR
modulators
Targacept has initiated a Phase I trial of TC-5619, a novel small molecule
that modulates the activity of the neuronal nicotinic receptor (NNR)
subtype, alpha7. The double-blind, placebo-controlled study is
designed to evaluate the safety, tolerability and pharmacokinetics of
TC-5619, with single escalating doses administered orally to healthy
volunteers.
TC-5619 was discovered using Targacept's proprietary drug design
technology known as Pentad and is the lead product candidate in its
alpha7 NNR programme. The alpha7 NNR is associated with a variety
of biological functions. In particular, it has been shown in animal
studies to be an essential regulator of both inflammation arising from
Page 19
GENERAL DEVELOPMENT NEWS
injury or infection and cognitive functions. Published in vitro studies
have also suggested that the alpha7 NNR plays a role in protecting
neuronal cells from deterioration and death, however Targacept has
not yet definitively selected the indication for which it will pursue the
development of TC-5619.
For details of further NNR research and a collaboration by Targacept,
see Neurodegenerative Disorders, Alzheimer's Disease - R&D Update;
Antidepressants, R&D Update; and General Development News,
Agreement News.
In addition...
NeuroSearch's development and licence partner, Abbott, has enrolled
and dosed the first patients in a Phase I study with the drug candidate,
ABT-560, which has treatment potential within a variety of CNS
disorders. The initiation of this study releases a milestone payment to
NeuroSearch.
ABT-560 is also an NNR modulator that has shown promise in
preclinical models relevant for the treatment of cognitive deficits.
According to the terms of the companies' licence agreement, Abbott
has all rights to ABT-560 and will finance all costs relating to the
development and commercialisation of the drug. NeuroSearch will
receive milestone payments, as well as royalties on Abbott's global
sales, if the drug is successfully commercialised.
Agreement News
Corcept enters microdosing study agreement with
Xceleron
Corcept Therapeutics has entered into an agreement for a human
microdosing study of one of its new chemical entities, a selective GR-
II antagonist, utilising Xceleron's accelerator mass spectrometry (AMS)
technology. GR-II antagonists have potential to be used in treating
numerous neurological disorders, including early dementia (including
Alzheimer's disease), psychosis associated with cocaine addiction and
the weight gain associated with antipsychotic medication.
Cortex initiated a discovery research programme to identify and
patent selective GR-II antagonists to develop a pipeline of products
for proprietary use. Three distinct series of GR-II antagonists
were identified that appear to be as potent as Corcept's Corlux
(mifepristone) in blocking cortisol, but unlike this product, they do
not block progesterone and other steroid receptors. The company
will evaluate the compound that develops particularly high plasma
and brain concentrations in an animal model, in a human microdosing
study using Xceleron's AMS technology. Under the terms agreed,
Xceleron will carry out the work using ultra-sensitive AMS, which
enables human drug-metabolite profiling to be performed in the early
stages of clinical development.
Penwest/Edison enter collaboration for neurological
disorders
Penwest Pharmaceuticals has entered into a research, development,
commercialisation and licence agreement with Edison Pharmaceuticals
for the treatment of neurological disorders resulting from defects in
cellular energy metabolism.
The initial focus of the collaboration is to pursue treatments for
orphan diseases of the mitochondria. Under the terms agreed,
Penwest has obtained exclusive worldwide rights to develop and
Page 20 ©
Espicom Business Intelligence
CNS Drug News
commercialise Edison's drug candidate, EPI-A0001, in all fields of use.
EPI-A0001 has been granted orphan drug status by the FDA for the
treatment of inherited mitochondrial respiratory chain diseases, and
Penwest intends to submit an IND application and commence clinical
development of the compound in early 2008. Additionally, Penwest
has the exclusive worldwide rights to develop and commercialise one
additional drug candidate to be selected from those identified by
Edison during the term of the sponsored research collaboration.
The financial terms of the agreement call for Penwest to provide
Edison with an up-front payment, a US$1 million loan and sponsored
research funding for the next 18 months. The aggregate total of these
payments and the loan is US$7.5 million. Penwest may, at its sole
discretion, extend the term of the sponsored research period by up to
an additional 18 months. The agreement also provides for payments
upon the exercise of certain options, success-based milestones
payments and royalties on net sales of any products commercialised
as a result of the collaboration.
Antares signs product development and licence
agreement with Jazz
Antares Pharma has signed a worldwide product development and
licence agreement with Jazz Pharmaceuticals, which demonstrates
the successful completion of a feasibility agreement that was initiated
between the companies in December 2005. The product candidate
underlying this agreement is being developed to treat a significant
CNS disorder and is based on Antares' proprietary ATD (advanced
transdermal delivery) system.
Under the terms agreed, Jazz will pay Antares up-front and product
development milestone payments, in addition to payments for any
future development activities. Antares will also receive royalties
on product sales upon commercialisation, including minimum
royalties. Total milestone and minimum royalty payments could add
up to US$16.5 million or more over the life of the agreement. Jazz
is responsible for the development and commercialisation of this
product candidate and will cover the costs of clinical trials, regulatory
filings, plus all manufacturing and marketing associated with the
product.
GSK forms US$1.5 billion CNS pact with Targacept
GlaxoSmithKline and Targacept have formed a strategic alliance that is
valued at up to approximately US$1.5 billion, to discover, develop and
market novel therapeutics that selectively target specified neuronal
nicotinic receptors (NNRs) to treat CNS conditions such as pain,
smoking cessation, obesity, addiction and Parkinson's disease. GSK will
participate in the alliance through its Center of Excellence for External
Drug Discovery.
Under the terms agreed, GSK will make an initial up-front payment of
US$35 million to Targacept, which includes an investment of US$15
million for the purchase of 1,275,502 shares of Targacept common
stock. In addition, Targacept is eligible to receive up to US$1.5 billion
in payments from GSK, contingent upon the achievement of specified
discovery, development, regulatory and commercial milestones across
five therapeutic focus areas, as well as tiered double-digit royalties
dependent on sales achieved.
The alliance includes Targacept's lead product candidates for pain, TC-
2696, which is currently in a Phase II trial for acute postoperative pain,
and TC-6499, a preclinical product candidate that is currently planned
for development for neuropathic pain. Targacept has retained an
option to co-promote the aforementioned drugs to specialists and
2nd August 2007
CNS Drug News CONFERENCE LISTINGS

hospital-based physicians in the US. In the alliance, Targacept will
utilise its proprietary Pentad drug-discovery technology to discover
novel small-molecule product candidates that target specified NNR
subtypes and will then develop the most promising product for each
therapeutic focus area through a proof-of-concept, Phase II trial.
Targacept is eligible to receive success-based progress milestones
from GSK as product candidates are advanced. Upon Targacept's
achievement of clinical proof-of-concept for a lead product candidate
for a particular therapeutic focus area, GSK would have an exclusive
option to license product candidates in development in the alliance
from that programme. GSK would then assume full responsibility for
funding of further clinical development and commercialisation on a
worldwide basis.
For details of further NNR research by Targacept, including the
initiation of clinical studies, see Neurodegenerative Disorders,
Alzheimer's Disease - R&D Update; Antidepressants, R&D Update; and
General Development News, R&D Update.

Conference Listings
CNS CONFERENCES - NOVEMBER 2007
DATE CONFERENCE TITLE CONTACT TEL/FAX/E-MAIL
1-3 10th International Conference on Continuing Professional Education, 601 Tel: 1 585 275 4392
the Mechanisms and Treatment of Elmwood Ave, Box 677 Rochester, NY Fax: 1 585 275 3721
Neuropathic Pain, Salt Lake City, UT, US 14642-8677, US E-mail: office@cpe.rochester.edu
2-4 Association of Anesthesiology Denise M Jones Tel: 1 847 825 5586
Program Directors/Society of Fax: 1 847 825 2085
Academic Anesthesiology Chairs E-mail: d.jones@asahq.org
Annual Meeting, Washington DC, US
8-11 5th International Congress on Vascular Meeting Organiser Tel: 41 229 080 488
Dementia, Budapest, Hungary E-mail: calendar@kenes.com
15-18 57th Annual Meeting of the Canadian CPA Head Office, 260-441 MacLaren, Tel: 1 613 234 2815
Psychiatric Association, Montréal, QC, Ottawa, ON, K2P 2H3, Canada Fax: 1 613 234 9857
Canada E-mail: agm@cpa-apc.org
17-18 1st Annual NYSORA (New York School Jo Watling Tel: 44 870 013 2930
of Regional Anesthesia) Europe Fax: 44 870 013 2940
Symposium, London, UK E-mail: jo.watling@optionsglobal.com
18-21 12th Asian-Australasian Society of Congress Secretariat, Fujita Health Tel: 81 562 93 9253
Neurological Surgeons/13th World University, 1-98 Dengakugakubo, Fax: 81 562 93 3118
Federation of Neurosurgical Societies Kutsukake-cho, Aichi-Ken 470-1192, Japan E-mail: aasns-office@umin.ac.jp
Interim Meeting, Nagoya, Japan
28/11-2/12 3rd International Congress on Brain & Global Events, 177 Egnatias str, 546 35 Tel: 30 2310 247 734/30 2310 247 743
Behaviour, Thessaloniki, Greece Thessaloniki, Greece Fax: 30 2310 247 746
E-mail: info@globalevents.gr
29/11-2/12 American Academy of Addiction American Academy of Addiction Tel: 1 401 524 3076
Psychiatry 18th Annual Meeting & Psychiatry, 345 Blackstone Blvd, 2nd Floor Fax: 1 401 272 0922
Symposium, Coronado, CA, US RCH, Providence, RI 02906, US E-mail: information@aaap.org
30/11-4/12 61st Annual Meeting of the American Meeting Organiser Tel: 1 860 586 7505
Epilepsy Society, Philadelphia, PA, US E-mail: csluboski@aesnet.org

NB: While every effort has been made to ensure that the above information is correct, CNS Drug News cannot accept any responsibility for any
decision taken on the information, which may be subject to change.

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2nd August 2007 ©
Espicom Business Intelligence Page 21
COMPANY INDEX
COMPANY INDEX
Abbott........................................................................................................................16, 19, 20
Academia Sinica.................................................................................................................... 9
Affiris........................................................................................................................................... 4
Akela Pharma........................................................................................................................16
Akzo Nobel............................................................................................................................16
Almirall....................................................................................................................................... 7
Amorfix Life Sciences......................................................................................................... 9
Antares Pharma...................................................................................................................20
Apkarian Technologies....................................................................................................17
AstraZeneca............................................................................................................................ 4
Avicena Group...................................................................................................................3, 8
Bar-Ilan Research & Development.............................................................................12
Baxter.......................................................................................................................................16
Bayer........................................................................................................................................... 7
Beijing Med-Pharm...........................................................................................................19
Biogen Idec.............................................................................................................................. 9
BioLineRx................................................................................................................................12
BioMS Medical....................................................................................................................... 6
Biovail.......................................................................................................................................12
Boehringer Ingelheim........................................................................................................ 1
Bristol-Myers Squibb........................................................................................................12
Cambridge Laboratories.................................................................................................. 8
Caraco Pharmaceutical Laboratories.......................................................................11
Cephalon................................................................................................................................11
Children’s Hospital Boston............................................................................................... 4
Chromos Molecular Systems.......................................................................................... 7
Columbia University....................................................................................................4, 13
Corcept Therapeutics.......................................................................................................20
Cortex Pharmaceuticals.................................................................................................... 3
deCODE genetics.......................................................................................................... 1, 10
Duke University.................................................................................................................1, 6
Durect......................................................................................................................................15
Edison Pharmaceuticals..................................................................................................20
Eisai............................................................................................................................................11
Elan.............................................................................................................................................. 3
Eli Lilly.......................................................................................................................................14
Emory University........................................................................................................... 1, 10
Endo Pharmaceuticals.....................................................................................................16
Ethypharm.............................................................................................................................19
Genaera...................................................................................................................................18
GlaxoSmithKline..........................................................................................................19, 20
Glenmark Pharmaceuticals............................................................................................. 7
GW Pharmaceuticals........................................................................................................... 6
Harvard Medical School.................................................................................................... 4
Howard Hughes Medical Institute............................................................................... 4
Hydra Biosciences..............................................................................................................16
Icagen.......................................................................................................................................17
Impax Laboratories............................................................................................................. 9
Intellect Neurosciences..................................................................................................... 9
Jazz Pharmaceuticals........................................................................................................20
Johns Hopkins......................................................................................................................19
Johnson & Johnson...........................................................................................................16
Kali Laboratories.................................................................................................................16
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Considered... clare_mills@espicom.com
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Page 22 ©
Espicom Business Intelligence
CNS Drug News
Kissei Pharmaceutical.....................................................................................................6, 8
Krka............................................................................................................................................14
Lucile Packard Children’s Hospital.............................................................................10
Meda AB..................................................................................................................................16
Medivation............................................................................................................................... 8
MedPointe.............................................................................................................................16
Merck & Co............................................................................................................................... 6
Merck KGaA............................................................................................................................. 3
Merck Serono......................................................................................................................... 3
Minrad......................................................................................................................................16
Nabi Biopharmaceuticals...............................................................................................17
Neurochem.........................................................................................................................5, 9
Neuroptix................................................................................................................................. 6
NeuroSearch.........................................................................................................................20
New York University............................................................................................................ 9
Newron Pharmaceuticals.......................................................................................... 3, 15
Northwestern University................................................................................................17
Novartis..................................................................................................................................... 5
Nuon Therapeutics..........................................................................................................6, 8
Nycomed................................................................................................................................15
Orexigen Therapeutics....................................................................................................18
Organon..................................................................................................................................16
Ortho-McNeil Pharmaceutical.....................................................................................16
Otsuka..................................................................................................................................7, 12
Par Pharmaceutical Companies..................................................................................16
Penwest Pharmaceuticals...................................................................................... 16, 20
Pfizer..................................................................................................................................16, 17
Proximagen Neuroscience.............................................................................................. 3
RxElite.......................................................................................................................................16
sanofi-aventis.................................................................................................................. 9, 19
Sepracor..................................................................................................................................11
Shire...........................................................................................................................................14
Southridge Technology..................................................................................................16
Southwestern Medical Center....................................................................................... 8
Stanford University............................................................................................................10
Summit...............................................................................................................................3, 18
SYGNIS Pharma....................................................................................................................10
Targacept......................................................................................................4, 12, 19, 20, 21
Tel Aviv University..............................................................................................................12
Tikvah Therapeutics.................................................................................................... 9, 17
University of California...................................................................................................... 6
University of Cambridge................................................................................................... 6
University of Edinburgh..................................................................................................14
University of Manchester...............................................................................................15
University of Miami............................................................................................................. 6
University of Minnesota..................................................................................................13
University of South Alabama.......................................................................................... 9
University of St Andrews.................................................................................................. 4
University of Texas............................................................................................................... 8
Vanderbilt University.......................................................................................................... 6
VASTox....................................................................................................................................... 3
Xceleron..................................................................................................................................20
2nd August 2007
CNS Drug News
Compound INdex
Abilify........................................................................................................................................12
ABT-560...................................................................................................................................20
acetaminophen...................................................................................................................16
Acomplia.................................................................................................................................19
Affitope AD01......................................................................................................................... 4
AL-02........................................................................................................................................... 8
Alzhemed................................................................................................................................. 5
aripiprazole............................................................................................................................12
AX200.......................................................................................................................................10
AZD3480................................................................................................................................... 4
BL-1020..............................................................................................................................12, 13
bupivacaine...........................................................................................................................15
bupropion.......................................................................................................................12, 18
BVF-033...................................................................................................................................12
calcium acetate...................................................................................................................17
cannabidiol.............................................................................................................................. 6
Champix..................................................................................................................................17
CHR-1103...............................................................................................................................7, 8
CHR-1201...............................................................................................................................7, 8
citalopram..............................................................................................................................12
Corlux.......................................................................................................................................20
creatine...................................................................................................................................... 3
CX717.......................................................................................................................................... 3
D-cycloserine........................................................................................................................13
Dimebon................................................................................................................................... 8
Empatic....................................................................................................................................18
enflurane................................................................................................................................16
EPI-A0001...............................................................................................................................20
eprodisate................................................................................................................................ 9
eszopiclone...........................................................................................................................11
Excalia.......................................................................................................................................18
Exelon......................................................................................................................................... 5
fentanyl....................................................................................................................................16
Fentanyl TAIFUN..................................................................................................................16
ICA-105665.............................................................................................................................17
isoflurane................................................................................................................................16
Kiacta.......................................................................................................................................... 9
lisdexamfetamine dimesylate.....................................................................................14
Lunesta....................................................................................................................................11
Lunivia......................................................................................................................................11
MBP8298................................................................................................................................... 6
mecamylamine....................................................................................................................12
mifepristone..........................................................................................................................20
Mirapex...................................................................................................................................... 1
modafinil.................................................................................................................................11
MSI-1436..................................................................................................................................18
nicotine.............................................................................................................................13, 17
NicVAX.....................................................................................................................................17
Nitoman.................................................................................................................................... 8
olanzapine.............................................................................................................................14
ondansetron.........................................................................................................................19
Opana.......................................................................................................................................16
Oxigon....................................................................................................................................... 9
oxymorphone......................................................................................................................16
PD-02.......................................................................................................................................... 3
PhosLo......................................................................................................................................17
Posidur.....................................................................................................................................15
pramipexole............................................................................................................................ 1
Provigil.....................................................................................................................................11
PRX4............................................................................................................................................ 3
ralfinamide......................................................................................................................15, 16
Rilutek......................................................................................................................................... 9
riluzole........................................................................................................................................ 9
2nd August 2007 ©
Espicom Business Intelligence
COMPOUND INDEX
rimonabant............................................................................................................................19
rivastigmine............................................................................................................................ 5
Rizaben...................................................................................................................................... 6
safinamide............................................................................................................................... 3
Sativex....................................................................................................................................6, 7
sevoflurane............................................................................................................................16
SMT 14400................................................................................................................................ 3
SMT C1100................................................................................................................................ 3
SMT D001................................................................................................................................. 3
SMT D002................................................................................................................................. 3
SMT D003................................................................................................................................. 3
Sojourn....................................................................................................................................16
StaphVAX................................................................................................................................17
sugammadex.......................................................................................................................16
TC-1734....................................................................................................................................... 4
TC-2216.....................................................................................................................................12
TC-2696....................................................................................................................................20
TC-5214.....................................................................................................................................12
TC-5619..............................................................................................................................19, 20
TC-6499....................................................................................................................................20
tetrabenazine......................................................................................................................... 8
tetrahydrocannabinol........................................................................................................ 6
tramadol.................................................................................................................................16
tramiprosate........................................................................................................................... 5
tranilast..................................................................................................................................6, 8
Tridmac....................................................................................................................................12
trodusquemine...................................................................................................................18
Ultane.......................................................................................................................................16
Ultracet....................................................................................................................................16
varenicline..............................................................................................................................17
Vyvanse...................................................................................................................................14
Xenazine................................................................................................................................... 8
Zalasta......................................................................................................................................14
Zimulti......................................................................................................................................19
Zofran.......................................................................................................................................19
zonisamide............................................................................................................................18
Zyprexa....................................................................................................................................14
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Published by Espicom Business Intelligence…

Anti-Infective Drug News - Published twice monthly, AIN reports the latest worldwide commercial developments in this high-value product area.
Price £545/$1095/€980
Autoimmune Drug Focus - Keeps you up-to-date with the latest advances in this important and high-value pharmaceutical area. Published monthly, ADF summarises
autoimmune disease research, as well as product submissions, approvals and collaborations. Price £545/$1095/€980
Cardiovascular Drug News - Published monthly, CVDN takes the hard work out of staying in touch with companies, products, alliances and research that are shaping the
global cardiovascular drug market. Price £545/$1095/€980
Cancer Drug News - Monitoring developments in world anticancer drug markets is becoming more and more vital as cancer remains one of the most resistant conditions.
Published weekly, CDN can help you stay in touch with the global cancer market. Price £575/$1195/€1035
Drug Delivery Insight - Published fortnightly, DDI is designed to keep you in touch with the latest developments in the rapidly expanding drug delivery market.
Price £575/$1195/€1035
Pharma Agreement News - Find out who is working with whom on what. Recent corporate restructuring has resulted in a number of collaborations. Published twice
monthly, PAN focuses on these agreements. Price £545/$1095/€980
Pharma Company Insight - Published weekly, PCI provides you with the latest news and developments involving pharmaceutical companies worldwide. Comprehensive
and easy to read, PCI is the time-efficient way to keep up with companies’ activities. Price £545/$1095/€980
Neuro Drug Focus - Neuro Drug Focus is a new business news service that will keep you fully updated with the latest developments in neurodegenerative product
registration, agreements and clinical trials. Price £545/$1095/€980
The Diabetes Report - Published monthly, TDR provides a comprehensive round-up of the latest developments in the diabetes therapy market. Price £545/$1095/EUR980
World Generic Markets - Published twice monthly, WGM is designed to keep executives and industry analysts in touch with the latest developments in the world of generic
pharmaceuticals. Price £575/$1195/€1035

All our newsletters are available by e-mail on the day of publication. Other formats include print and web access.

Ordering CNS Drug News

CNS Drug News is available in print, e-mail and web formats. The web version provides you with a daily updated news service, while the pdf & paper issues provide a twice-monthly digest. One-to-one live online demonstrations available!
An annual subscription costs just £575/$1195/€1035 for a paper or e-mail subscription, or a single-user web licence.

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