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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


colleagues from Emory University, have discovered the first variant in
the sequence of the human genome ever linked to risk of restless legs
Eisai enters partnership for Sepracor’s eszopiclone syndrome (RLS) and periodic limb movements (PLMs). The SNP was
Page 11 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,
GSK forms US$1.5 billion CNS pact with Targacept 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 CNS Drug News

TABLE OF CONTENTS
Will discovery be a breakthrough for MS?.............................................................................1 Psychotic Disorders.......................................12
NEURODEGENERATIVE DISORDERS.......................3 R&D Update.............................................................................................12
Parkinson's Disease - R&D Update........................................................3 BL-1020 shows antipsychotic efficacy; enters Phase II trial in schizophrenia......................12
Enrolment on target in Phase III trial of PD-02......................................................................3 Drug may help people with OCD; to be tested on smokers..................................................13
Phase III PD data for safinamide delayed..............................................................................3 Children show sustained improvement after ADHD treatment...........................................13
Proximagen awarded MJFF grant to pursue gene therapy approach for PD......................3 Progressive grey matter loss discovered in BPD....................................................................14
VASTox re-named as Summit.................................................................................................3 Product News........................................................................................14
Alzheimer's Disease - R&D Update........................................................3 EMEA recommends authorisation of first generic medicine for human use.......................14
Cortex to resume enrolment in CX717 study at all dose levels.............................................3 Shire's Vyvanse available in US pharmacies..........................................................................14
Affiris begins clinical testing of AD vaccine...........................................................................4 Analgesics/Anaesthetics................................15
Researchers shed light on how diet and exercise enhance longevity..................................4 R&D Update.............................................................................................15
AstraZeneca initiates Phase IIb trial of AZD3480 in AD.........................................................4 Study may accelerate research into next generation of painkillers.....................................15
Compound reverses signs of AD.............................................................................................4 Durect reports positive Phase IIb Posidur data.....................................................................15
Neurochem granted fast track designation for Alzhemed...................................................5 Newron reveals additional analyses of ralfinamide Phase II study......................................15
Product News........................................................................................5 Meda agrees to acquire MedPointe.......................................................................................16
Novartis' Exelon patch recommended for European approval............................................5 Akela completes enrolment in Phase IIb trial of Fentanyl TAIFUN.......................................16
Agreement News...................................................................................6 Product News........................................................................................16
Neuroptix receives milestone payment from Merck in AD collaboration............................6 Ortho-McNeil/Par settle Ultracet patent litigation...............................................................16
Multiple Sclerosis - R&D Update..........................................................6 Organon's MAA for sugammadex accepted for review........................................................16
Research identifies first new MS gene in 30 years................................................................6 RxElite launches generic sevoflurane in the US.....................................................................16
Nuon raises funds to advance tranilast development..........................................................6 US PTO allows Opana ER-related patent application............................................................16
BioMS' RRMS trial receives positive DSMB review................................................................6 Agreement News...................................................................................16
Product News........................................................................................6 Hydra signs global TRPV3 collaboration with Pfizer..............................................................16
GW withdraws European application for Sativex in MS spasticity......................................6 Tikvah enters licensing agreement with Apkarian...............................................................17
Agreement News...................................................................................7
Glenmark purchases rights to CHR-1103 and CHR-1201 from Chromos..............................7 Therapies to Treat Substance Dependence....17
Nuon and Kissei complete tranilast agreement....................................................................8 R&D Update.............................................................................................17
Other Neurodegenerative Disorders - R&D Update...........................8 Nabi creates pharmaceuticals business unit.........................................................................17
TBZ protects brain cells in HD model.....................................................................................8 Drug may help people with OCD; to be tested on smokers..................................................17
Avicena to proceed with confirmatory Phase III ALS trial.....................................................8 Product News........................................................................................17
First patient treated in Phase II trial of Dimebon for HD.......................................................8 UK's NICE issues guidance on Champix for smoking cessation.............................................17
Intellect reports positive safety data from Phase Ia Oxigon trial.........................................9 Anti-Epileptics................................................17
Product News........................................................................................9 R&D Update.............................................................................................17
Neurochem receives second FDA approvable letter for Kiacta in AA amyloidosis..............9 Icagen files IND for novel epilepsy compound......................................................................17
Rilutek patent ruled not invalid.............................................................................................9
Agreement News...................................................................................9 Eating Disorders.............................................18
Biogen Idec to exercise first milestone investment in ALS collaboration with Amorfix.....9 R&D Update.............................................................................................18
Tikvah/Academia Sinica enter licensing agreement for neurodegenerative disorders.....9 Preclinical data confirm trodusquemine's potential for obesity..........................................18
Orexigen reports positive Phase IIb data with Empatic for obesity.....................................18
Cerebrovascular Disorders..........................10 Product News........................................................................................19
R&D Update.............................................................................................10 CHMP recommends upgraded warnings for Acomplia........................................................19
SYGNIS completes Phase IIa study of AX200 in stroke..........................................................10
Drugs used in Nausea & Vertigo.....................19
Anxiolytics/Sleep Disorders..........................10 Agreement News...................................................................................19
R&D Update.............................................................................................10 Shanghai Ethypharm signs ondansetron licence agreement with Beijing Med-Pharm....19
deCODE discovery points to new RLS treatment approach..................................................10
Severe trauma may affect children's brain function.............................................................10 General Development News...........................19
Product News........................................................................................11 R&D Update.............................................................................................19
Sepracor submits Lunivia MAA..............................................................................................11 Study further links addiction and memory...........................................................................19
Caraco receives tentative FDA approval for generic Provigil................................................11 Targacept/Abbott initiate Phase I trials of NNR modulators................................................19
Agreement News...................................................................................11 Agreement News...................................................................................20
Eisai enters partnership for Sepracor's eszopiclone..............................................................11 Corcept enters microdosing study agreement with Xceleron..............................................20
Penwest/Edison enter collaboration for neurological disorders.........................................20
Antidepressants.............................................12 Antares signs product development and licence agreement with Jazz..............................20
R&D Update.............................................................................................12 GSK forms US$1.5 billion CNS pact with Targacept...............................................................20
Add-on mecamylamine treatment shows positive effects in depression..........................12
Product News........................................................................................12 Conference Listings........................................21
Abilify sNDA granted priority review by FDA.........................................................................12 COMPANY INDEX.................................................22
Biovail receives non-approval letter from FDA for BVF-033.................................................12
Compound INdex..............................................23

Page  ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News NEURODEGENERATIVE DISORDERS

NEURODEGENERATIVE DISORDERS
and could restore normal brain function to patients, reversing the
Parkinson's Disease - R&D Update difficulties in movement that characterise this illness. Proximagen's
preclinical studies have shown that this neuroprotective protein is
Enrolment on target in Phase III trial of PD-02 implicated in the control of many mechanisms associated with the
degeneration of neurons. The company has demonstrated that even
The Phase III efficacy trial of Avicena Group's lead Parkinson's disease in very low concentrations, PRX4 derivatives act as highly-potent
(PD) drug candidate, PD-02 (creatine), has enrolled 288 patients in inhibitors of neurodegeneration in neuronal cells.
the first three months. The study, which is sponsored by the National
Institute of Neurological Disorders and Stroke (NINDS), is evaluating VASTox re-named as Summit
PD-02's potential to slow the progression of PD.
VASTox has changed its name to Summit. The new name, which was
This trial will enrol over 1,720 patients at more than 50 sites in the US approved by shareholders on 19th July, is aimed at encapsulating the
and Canada, making it one of the largest PD trials ever conducted. company's ambitions, as well as providing an identity that has the
Avicena previously announced that the NINDS had awarded a grant flexibility to accommodate the future growth and development of the
for the study. As part of the company's collaboration with the NINDS, business.
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 The company's lead drug candidates, which are in Phase I testing
for the approval of PD-02 as a treatment for PD. Avicena also holds for sialorrhoea and seborrhoea in Parkinson's disease, respectively,
intellectual property rights for the use of PD-02 in PD. will now be known as SMT D001 (formerly DL06001) and SMT
D002 (formerly DL06003). The new names for Summit's preclinical
Data from Phase II efficacy trials conducted at the University of candidates are: SMT C1100 (formerly VOXC 1100), for Duchenne
Rochester showed PD-02 to be safe and well tolerated. Furthermore, muscular dystrophy; SMT D003 (formerly DL06005), for glaucoma; and
findings demonstrated the compound's potential to slow the rate of SMT 14400 (formerly VOX 14400) for cancer.
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 Alzheimer's Disease - R&D Update
disease.
Cortex to resume enrolment in CX717 study at all dose
Phase III PD data for safinamide delayed levels

Newron Pharmaceuticals has confirmed that the disclosure of data Following a review of the Ampakine CX717 data package sent to the
from a 12-month extension of a Phase III trial with safinamide, an FDA's Division of Neurology Products (DNP) on 17th April, the Agency
orally-administered alpha-aminoamide derivative, in early Parkinson's has given Cortex Pharmaceuticals the go-ahead to immediately
disease (PD) patients will be delayed; the information had been resume enrolment in the CX717 Alzheimer's disease (AD) PET scan
expected by the end of June. Merck Serono (Merck KGaA) has exclusive study at all requested dose levels. The study was originally designed
worldwide rights to develop, manufacture and commercialise with doses of 200, 600 and 1,200mg to be administered to patients,
safinamide in PD, Alzheimer's disease, other cognitive disorders and however, the FDA previously limited the dose levels such that the 600
restless legs syndrome. and 1,200mg doses could not be administered. The new protocol
approved by the Agency allows a return to the original dose levels.
Proximagen awarded MJFF grant to pursue gene
therapy approach for PD 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
Proximagen Neuroscience has been awarded a Novel Approaches
performed in mild-to-moderate AD patients who are drug naïve or
to Drug Discovery for Parkinson's Disease grant by the Michael J Fox stabilised on cholinesterase inhibitors at the University of Michigan
Foundation (MJFF) for Parkinson's Research to pursue research into Medical Center. In animal studies, cholinesterase inhibitors such as
the development of a novel gene therapy approach for the treatment Aricept (donepezil) and Reminyl (galantamine) appear to enhance the
of Parkinson's disease (PD). effects of CX717.

The MJFF is providing the funding under an initiative established The earlier dose limitations imposed by the FDA were related to
through leadership funding from Elan. Under the terms of the concerns over data from preclinical studies rather than any findings
agreement, Elan is given a first option to obtain an exclusive from clinical trials. The DNP plans to continue its review of the data
worldwide commercial licence to the programme. package, but saw no reason to not permit the full resumption of
the current AD PET scan study. Cortex will continue to have further
The funding is to continue Proximagen's PRX4 research and discussions with the DNP regarding the previously-submitted
development programme, which centres around a gene that toxicology package and additional requirements may be requested
produces a neuroprotective protein present in healthy individuals, but by the FDA.
lacking in patients with PD. PRX4 is being developed using viral vector
delivery technology, which delivers genetic material directly into brain Cortex intends to file a second IND for CX717 with the Division of
cells. The combined neuroprotective gene and viral vector will be Psychiatry Products during the third quarter of 2007, to allow the
targeted to an area of the brain that degenerates in PD. If successful, company to initiate a Phase IIb study evaluating the compound for the
the treatment may prevent the disease from causing further damage treatment of attention deficit hyperactivity disorder.

2nd August 2007 ©


Espicom Business Intelligence Page 
NEURODEGENERATIVE DISORDERS CNS Drug News
Affiris begins clinical testing of AD vaccine This reduces the amount and duration of insulin secretion needed
to keep glucose under control after eating, therefore, the brain is
Affiris' Alzheimer's disease (AD) vaccine, Affitope AD01, has entered exposed to less insulin. Since insulin turns on Irs2 in the brain, that
the clinical phase of its development. Up to 24 patients with AD means lower Irs2 activity, which the researchers have now linked to
are to be vaccinated, with the aim of this initial Phase I trial being to longer lifespan in the mouse.
demonstrate the vaccine's safety and suitability for human use.
The investigators are planning subsequent studies to better
Affiris has developed the vaccine from patented Affitope technology, understand how healthy ageing and lifespan are co-ordinated by
which is based on mimotopes and allows customised vaccines to be Irs2 signalling pathways in the body and brain. Scientists now have
manufactured cost-effectively. The company's approach protects a greater appreciation that obesity, insulin resistance and high
brain cells and only combats the disease-causing amyloid beta. blood insulin levels are connected to AD, Huntington's disease and
dementias in general. These researchers speculate it is possible that
The vaccine is being administered at the Vienna General Hospital in in people who are genetically predisposed to these disorders, too
Austria, to patients who have reached the mild-to-moderate disease much insulin overactivates Irs2 in the brain and accelerates disease
stage. Patients will be vaccinated four times over a period of three progression. Thus, insulin resistance and higher insulin levels might be
months, and the safety and suitability of the vaccine will be analysed the environmental influences that promote these diseases.
over six months.
AstraZeneca initiates Phase IIb trial of AZD3480 in AD
Researchers shed light on how diet and exercise
enhance longevity Targacept's strategic collaborator, AstraZeneca, has initiated a Phase
IIb trial of AZD3480 (TC-1734) in Alzheimer's disease (AD).
Through studying long-lived mice, Howard Hughes Medical Institute
researchers at Children's Hospital Boston and Harvard Medical School This double-blind, placebo-controlled study is being conducted at
have found that sensible diet, exercise and weight control extend sites in Western and Eastern Europe, as well as Canada. The trial design
life by reducing signalling through a specific pathway in the brain. provides for approximately 500 patients with mild-to-moderate AD
The investigators, whose work was published in the 20th July issue to be randomly assigned to one of three dose groups of AZD3480, an
of PNAS (2007;317:369-372), believe that their findings underscore active comparator or placebo, and to be dosed over a 12-week period.
the importance of maintaining a healthy lifestyle and may also The trial is expected to complete by the end of 2008.
offer promising research directions for understanding and treating
Alzheimer's disease (AD) and diabetes. AZD3480 acts selectively on neuronal nicotinic receptors (NNRs) and
has been evaluated in 12 clinical trials in approximately 540 subjects.
The insulin-like signalling pathway is known to govern growth and In a previous Phase IIb trial conducted by Targacept in age-associated
metabolic processes in cells throughout the body. The pathway is memory impairment, AZD3480 achieved statistically significant results
activated when insulin and insulin-like growth factor-1 switch on on all of the primary endpoints, demonstrating cognitive-enhancing
insulin receptor substrates (Irs). Other researchers had shown that effects in memory-impaired older adults. Furthermore, AstraZeneca is
reducing the activity of the pathway in Caenorhabditis elegans and scheduled to begin dosing in a Phase IIb trial of AZD3480 for cognitive
Drosophila extends lifespan, however, based on previous work, the deficits in schizophrenia in August.
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 For details of further NNR research and a collaboration by Targacept,
the body to control blood glucose, plus it promotes growth, survival see Antidepressants, R&D Update; General Development News, R&D
and insulin secretion from beta cells. Update; and General Development News, Agreement News.

In earlier work, the researchers had found that knocking out both Compound reverses signs of AD
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 Biologists at the University of St Andrews in the UK have developed a
researchers knocked out only one copy of the gene, they found that
compound, which is capable of blocking a nerve cell interaction that
the mice lived 18 per cent longer than normal mice.
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
Because reducing insulin-like signalling in the neurons of roundworms
with the disease. Dr Frank Gunn-Moore's team, in collaboration with
and fruitflies extends their lifespan, the researchers decided to
Columbia University researchers in the US, successfully reversed a sign
examine what would happen if one or both copies of the Irs2 gene
were knocked out only in the brains of mice. for the progression of AD and prevented the death of brain cells.

Mice lacking one copy of the Irs2 gene in brain cells also showed an In AD, the amyloid protein inflicts damage by interacting with an
18 per cent longer lifespan and the near complete deletion of brain enzyme called ABAD (amyloid beta alcohol dehydrogenase) and
Irs2 had a similar effect. Further, the animals lived longer, even though releasing toxic substances that kill brain cells. Gunn-Moore's research,
they had characteristics that should shorten their lives, including being which was published in the June issue of Molecular and Cellular
overweight, hyperinsulinaemic and glucose intolerant. However, Neuroscience (2007;35:377-382) and carried out in the laboratory using
both sets of Irs2-knockout mice exhibited other characteristics that a model of the disease, initially focused on developing the 3D shape of
marked them as healthier. They were more active as they aged and ABAD and understanding how amyloid attaches itself to the structure.
after eating, the animals' brains showed higher levels of the potent
antioxidant enzyme, superoxide dismutase. Patients with AD produce too much amyloid and ABAD in their brains.
Based on their knowledge of ABAD, the researchers produced an
These findings put a mechanism behind what is already known, that inhibitor that can prevent amyloid attaching to it in a living model and
eating a good diet and exercising will keep a person healthy; diet, showed that it is possible to reverse some of the signs associated with
exercise and lower weight keep peripheral tissues sensitive to insulin. the disease.

Page  ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News NEURODEGENERATIVE DISORDERS

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
Clinical Biomarkers Forum
Harnessing the potential of biomarkers from translational
research, throughout clinical trials
The FDA has designated Neurochem's investigational product
candidate, Alzhemed (tramiprosate), as a fast track product for the 13th – 14th September 2007, Prague
treatment of Alzheimer's disease.
Delegates already attending have brought their queries to the
As previously reported, Neurochem requested a meeting with table, and will benefit from case study presentations and
the FDA, which is now scheduled for August, with the Division of roundtable discussions on:
Neurology Products. The goal of this meeting is to have a discussion
on the tramiprosate Phase III programme and present an update on
ƒ Maximising the potential of biomarkers across drug
the work accomplished, to date, on the North American Phase III trial.
Neurochem will also seek the FDA's feedback and validation on the development
next steps that would be acceptable to the Agency, especially with
ƒ How companies have lowered attrition, risk and costs
respect to the statistical models.
ƒ Development of surrogate biomarkers and companion
In relation to the ongoing European Phase III trial, patient screening diagnostics for the pharmaceutical industry
activities will stop in August, as Neurochem has exceeded its original
patient enrolment objectives. However, in light of the information ƒ How can we translate pre-clinical results into humans?
and experience gained from the North American trial, the company ƒ Have companies seen a real reduction in timeframes as a
is presently considering modifications that would need to be made to
the design of the European study. direct result of biomarker implementation?
ƒ When will regulations catch up with innovation?....And

Product News much more!

Novartis' Exelon patch recommended for European What is your number one concern or question relating to the
approval performance of biomarkers in R&D? Make sure that it is raised
and answered at this unique event by registering today.
A patch that delivers Novartis' Exelon (rivastigmine) has received
a positive opinion for treating mild-to-moderately severe forms To download a brochure, visit our website at:
of Alzheimer's disease (AD) from the EMEA's CHMP and the EC is www.clinicalbiomarkers.net
expected to issue a decision on the product within three months.

Since 1997, Exelon has been used to treat mild-to-moderate AD in Our expert panel of speakers includes:
more than 70 countries. The FDA approved Exelon Patch on 6th July,
for the treatment of both mild-to-moderate AD and Parkinson's x Dr Stefan Scherer, Biomarker Program Leader, AVASTIN, F.
disease dementia. The EU positive opinion was based on results Hoffmann-La Roche
from the international IDEAL (Investigation of Transdermal Exelon Dr. Stefan Sultana, Translational Medicine Leader for GU
in ALzheimer's disease) trial, which showed that patients receiving Therapeutic Area, Pfizer
the patch demonstrated improved memory, overall functioning x Dr. Orest Hurko, Assistant Vice President, Translational
and ability to perform everyday activities compared to those taking Research, Wyeth
placebo. Clavert Louden, Head, Department of Pathology Assessment,
AstraZeneca
The patch is applied to the back, chest or upper arm, and provides x Dr. Thomas Senderovitz, Vice President Global Clinical
smooth and continuous delivery of medication through the skin over Pharmacology & Experimental Medicine, UCB Pharma S.A.
24 hours, with the potential for improved efficacy. A key attribute x Dr. Chetan Lathia, Director, Global Clinical Pharmacology,
of the patch is a sharp reduction in gastrointestinal side effects Bayer
commonly seen with oral forms of the cholinesterase inhibitor class x Dr. Stefan Otto Muller, Senior Toxicologist, Merck Serono
of drugs. In a clinical trial, these side effects were greatly reduced, KGAA
with three-times fewer reports of nausea and vomiting than with the x Dr. Eric Blomme, Project Leader, Cell and Molecular
capsule form of the drug. Toxicology, Abbott

Designed with compliance in mind, the patch was preferred to TO REGISTER YOUR PLACE
capsules by >70 per cent of caregivers in a clinical study as a method of Go online at www.clinicalbiomarkers.net
drug delivery because it helped them follow the treatment schedule, or
interfered less with their daily life and was easier to use overall than an Contact Paul Osmond: +44 (0)20 7880 0000
oral medication. Email: paul_osmond@osneymedia.co.uk

2nd August 2007 ©


Espicom Business Intelligence Page 
NEURODEGENERATIVE DISORDERS CNS Drug News
Nuon raises funds to advance tranilast development
Agreement News
Nuon Therapeutics has completed a US$5 million series A financing,
Neuroptix receives milestone payment from Merck in capital that will support clinical studies of its orally-active lead
AD collaboration compound, tranilast, targeting multiple sclerosis (MS), rheumatoid
arthritis (RA) and pain.
Neuroptix has been granted a US$1 million milestone payment under
its Alzheimer's disease (AD) diagnostic collaboration with Merck Kissei Pharmaceutical has marketed tranilast (under the brandname
& Co. Under the agreement, which was announced in December Rizaben) in Japan and Korea for bronchial asthma since 1982.
2006, Neuroptix provides Merck with access to its laser eye-scanning Indications for keloid and hypertrophic scar were added in 1993. In
technologies, which in preclinical studies, have detected AD-related addition, a Rizaben eye drop was launched in 1995 in these markets
amyloid protein aggregates in the lens of the eye. The quantitative and is widely used for allergic conjunctivitis. Tranilast is thought to act
technique has potential for the early detection and monitoring of AD in these diseases by inhibiting the release of chemical inflammatory
progression. 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
Multiple Sclerosis - R&D Update conducted wide-ranging preclinical testing of tranilast, with the
compound showing improvement in an animal model of MS.
Research identifies first new MS gene in 30 years
The funding will enable Nuon to advance tranilast through the next
A gene has been identified that may hold the promise of guiding phase of clinical development, as well as support the discovery and
future research into therapies for multiple sclerosis (MS). According development of additional compounds. Initially, the funds will be used
to its discoverers, this is the first major genetic advance in 30 years for to develop and protect the company's intellectual property, hire staff,
understanding the disease. secure supply of drug product, undertake related licensing and open
an FDA IND application.
The finding, which was published in the 29th July online edition of
Nature Genetics (10.1038/ng2103), demonstrates that a functional For details of Nuon completing a licensing, supply and collaboration
gene variant on chromosome 5 was associated with an increased agreement with Kissei for tranilast, see Agreement News.
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 BioMS' RRMS trial receives positive DSMB review
gene.
The independent Data Safety Monitoring Board (DSMB) for BioMS
First author, Dr Simon Gregory, and his colleagues at Duke University Medical's Phase II MINDSET-01 trial of MBP8298 in patients with
Medical Center were joined by researchers from the University of relapsing-remitting multiple sclerosis (RRMS) has completed a safety
California, San Francisco and the University of Cambridge in the UK, analysis and recommended that the trial continue as per the protocol.
who spearheaded the collection of MS populations over many years, This was the first of several regularly-scheduled reviews by the DSMB
and the University of Miami and Vanderbilt University. The same team that will occur over the duration of the study.
was also involved in another paper replicating similar findings from a
whole-genome analysis, which was published in the 29th July online MINDSET-01 is a 15-month, double-blind, placebo-controlled trial. The
edition of the NEJM (10.1056/NEJMoa073493). objectives of the study, which is fully enrolled with approximately 215
patients at 24 sites in six countries, are to demonstrate the safety and
Previously-discovered MS genes were all located in an area of efficacy of MBP8298 versus placebo, as measured by relapse rate, MRI
chromosome 6 involved in the major histocompatibility complex. activity and disease progression.
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.
Product News
GW withdraws European application for Sativex in MS
The scientists used the technique of genomic convergence, in which spasticity
they took the results of many studies looking for common elements.
From studies involving patients and their families in the US and UK,
GW Pharmaceuticals has chosen to withdraw its current regulatory
they analysed more than 7,000 DNA samples from patients with
application for Sativex, a cannabis-derived, oro-mucosal spray
confirmed MS and those without the disease. composed primarily of tetrahydrocannabinol and cannabidiol, in
Europe, but expects to resubmit an application for approval in 2008.
After winnowing down 28 candidate genes to the IL-7R gene, the This follows constructive and detailed discussions with regulatory
researchers then tested their findings on a different set of patient authorities in which they have provided a clear path to approval for
populations to confirm the results. They showed that the same genetic Sativex in the treatment of multiple sclerosis (MS) spasticity.
change in IL-7R increased the risk of MS to a very similar extent in four
different populations. In September 2006, GW filed an application for Sativex under the
decentralised procedure in four European countries (the UK, Spain,
According to Gregory, as research builds upon the altered function Denmark and the Netherlands) for the relief of MS spasticity. The
of IL-7R, the mechanisms involved in the development of MS will be company has been able to successfully resolve all the major questions
unlocked, which may lead to novel treatments for the disease or the raised by the regulators during this process except one, and at a recent
identification of targets for new therapies. meeting with the UK assessors, it became clear that this outstanding

Page  ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News NEURODEGENERATIVE DISORDERS

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.
23 - 25 October 2007
The regulator's outstanding clarification relates to the fact that in
The Royal Garden Hotel
London, United Kingdom
a clinical trial context, the benefit obtained by "responders" can
be masked by looking at the mean improvement across the entire
CNS disorders: today’s science to
studied patient population, which comprises both responders and tomorrow’s market
non-responders. The regulators therefore wish to be able to identify
Sativex responders in the first four weeks of treatment and to confirm CNS disorders are one of the leading causes of mortality
that the improvements gained by such responders over a further 12- worldwide. According to reports, neurological disorders
week period is significantly greater than placebo. affect over 1 billion people globally. The prevalence of these
disorders is rising, principally driven by a global aging
As part of the current regulatory process, GW performed analyses of
population. However there is a lack of blockbuster drugs and
existing data showing that responders can be reliably identified after
four weeks and that after 12 weeks, the difference from placebo is
targeted therapies to cater for the number of patients and
clinically important and highly statistically significant (p=0.015). The range of disorders.
regulators view this as acceptable evidence of efficacy in principle,
NeuroDrug 2007 focuses on drug discovery and development
but consider these analyses technically to be post hoc since they were
performed at the regulator's request following completion of the trials.
across the CNS sector. Our agenda focuses on novel
They require such data to be produced as part of a prospectively- therapeutic targets for neurological, neurodegenerative and
planned analysis and hence GW will undertake an additional study to psychiatric disorders. Key learning include case studies on
reconfirm this result prior to resubmitting its regulatory application. cutting edge drugs and therapies, lead optimisation, novel
biomarkers and imaging, latest approaches to drug delivery
The regulators have given GW clear guidance as to the design of and crossing the blood brain barrier.
the required further study, which differs from a conventional Phase
III design. The study is expected to start recruiting patients in the The best mix of expert speakers from the
pharmaceutical and biotech sectors
next few months, with the results due in the second half of 2008.
The regulators have specified a novel "enriched design," which first
Our senior level speakers come from world class
identifies responders over a four-week period and then focuses on
pharmaceutical companies, leading biotechs and unrivalled
analysing the effect of Sativex versus placebo on those responders
over a further period of time. GW's clinical plans for the next 12
medical research centres. Represented companies include
months already included a further MS spasticity trial, therefore the GlaxoSmithKline, AstraZeneca, Johnson & Johnson, Wyeth,
regulator's specific design requirements will be incorporated into this Eli Lilly, Boehringer Ingelheim, Schering-Plough, UCB
planned study. Pharma, Lundbeck, Pierre Fabre, Otsuka Maryland
Medicinal Laboratories, Oxford BioMedica and the
There are two potential opportunities for early resubmission in Europe Foundation for the NIH. 90% of speakers are CxO’s,
next year. In the indication of MS neuropathic pain, a second pivotal Therapeutic Area Heads, Directors or Presidents. Advances
Phase III trial is expected to complete in early 2008, which could in CNS drug discovery and development are best achieved
lead to a regulatory filing in this indication at that time. Since this is a through knowledge sharing and collaborations.
distinct indication from MS spasticity, the outstanding issue identified
as part of this recent application would not be relevant. In the event Eli Lilly explains why this is a must
that GW does not submit for this indication, the second opportunity attend event
is to resubmit for MS spasticity later in 2008, following completion of
the new study. "Neurodrug 2007 offers an excellent insight into multiple
aspects of CNS drug discovery. The meeting has topics that
Elsewhere, the company anticipates receiving final regulatory approval relate to most CNS disorders such as new technology, drug
in Canada for the cancer pain indication in the coming weeks and its delivery, biomarkers and more specific focused topics such
first large-scale clinical trials in the US are scheduled to commence in as small molecule, viral delivery and stem cell approaches to
late summer. To date, GW has entered into Sativex licence agreements treat neurodegeneration. The varied approaches taken for
with Otsuka in the US, Bayer HealthCare in the UK and Canada, and certain diseases should make an interesting meeting with
Almirall in Europe (excluding the UK). opportunity to discuss and network".

Dr Michael J. O'Neill, Research Advisor,


Agreement News Neurodegeneration Drug Team, Eli Lilly

Glenmark purchases rights to CHR-1103 and CHR-1201


from Chromos 3 easy ways to register
Online: www.lifescienceworld.com/2007/neuro
Glenmark Pharmaceuticals has completed its purchase of Chromos Email: julie.phillips@terrapinn.com
Molecular Systems' two new biological entities (NBEs), CHR-1103 and
CHR-1201, which are humanised therapeutic monoclonal antibodies
Tel: +44 (0) 207 539 4336
(MAbs). Under the terms of the transaction, Glenmark has purchased Event code: 14/1318 / Espicom
all rights to the two products, as well as rights to use Chromos'

2nd August 2007 ©


Espicom Business Intelligence Page 
NEURODEGENERATIVE DISORDERS CNS Drug News
proprietary ACE System technology for cell line development for use The researchers conducted various co-ordination tests on both
with respect to the two NBEs. Glenmark holds the worldwide rights normal and genetically-manipulated mice. Engineered mice given
for further development, registration and commercialisation of these a drug that increased brain dopamine levels performed worse on
products. Further terms were not disclosed. these tasks, while TBZ protected against this effect. Most importantly,
TBZ appeared to significantly reduce cell loss in the striatum of the
The NBEs are part of a validated class of drugs known as selective engineered mice.
adhesion molecule inhibitors. CHR-1103 is a broad anti-inflammatory
agent with a novel mechanism of action that is initially being More research is needed to determine whether this protective effect
developed to treat acute multiple sclerosis. Glenmark plans to initiate might also be present in humans and if at-risk people would benefit
Phase I trials in 2008 and complete this stage of development with from the drug. However, senior author, Dr Ilya Bezprozvanny, believes
CHR-1103 by March 2009. CHR-1201 is an antithrombolytic humanised that clinical trials would be difficult, because they require many
MAb that Glenmark initially plans to develop to treat acute stroke; the participants and there is no easy way to score the effectiveness of a
company plans to start Phase I development with CHR-1201 by March presymptomatic drug. Thus, his future studies in animals will look
2009. at the effectiveness of TBZ given just after initial symptoms have
developed, a situation that simulates what would probably happen in
Nuon and Kissei complete tranilast agreement a human trial.

Nuon Therapeutics has completed a licensing, supply and Editor's note: Cambridge Laboratories has worldwide rights to TBZ and
collaboration agreement for tranilast with Kissei Pharmaceutical. markets the product itself in the UK and Eire, and through marketing
The agreement will enable Nuon to advance tranilast through the partners in Europe and other global markets.
next phase of clinical development, while giving Kissei the exclusive
option right for research, development and marketing of tranilast Avicena to proceed with confirmatory Phase III ALS
in Japan and Korea in the autoimmune disease field, including trial
multiple sclerosis (MS). The partnership will enable multiple Phase II
development programmes. 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
The terms of the agreement include provisions for Kissei to treatment of amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease).
supply tranilast to Nuon for clinical trials and license Nuon-related
intellectual property (IP) on the compound. The agreement also Two completed Phase III studies demonstrated a positive trend
establishes a collaborative relationship between the companies for towards increased survival at nine months and Avicena will be
the development of additional portfolio products. Nuon has licensed analysing the data at the 18-month time point to confirm a longer-
and developed worldwide IP for the use of tranilast to treat MS, term survival benefit. These data will be used to support the new
rheumatoid arthritis, pain and other indications. Phase III study, which is planned to commence in 2008 and will be
designed to evaluate AL-02's potential to increase survival.
For details of Nuon raising funds to advance tranilast's development,
see R&D Update. First patient treated in Phase II trial of Dimebon for
HD

Other Neurodegenerative Disorders The first patient has been treated in Medivation's Phase II trial of
- R&D Update 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
TBZ protects brain cells in HD model
compound and placebo.
University of Texas Southwestern Medical Center researchers have
Medivation is conducting the trial in collaboration with the
found that a drug used in some countries to treat the symptoms
Huntington Study Group (HSG). The Phase II portion will be
of Huntington's disease (HD) prevents the death of brain cells in
conducted at approximately 17 HSG sites in the US and Europe, and
mice genetically engineered to mimic the hereditary condition. The
is a randomised, placebo-controlled, double-blind evaluation of the
research, which was published in the 25th July issue of the Journal
safety and preliminary efficacy of Dimebon in 90 patients with HD
of Neuroscience (2007;27:7899-7910), sheds light on the biochemical
after three months of dosing. The primary efficacy endpoint of the
mechanisms involved in the disease and suggests new avenues
Phase II portion is the UHDRS and Medivation expects to report study
of study for preventing brain cell death in at-risk people before
data in the first half of 2008. According to the company, the results
symptoms appear.
from the Phase I portion of the study have allowed it to move forward
to the preliminary efficacy phase.
The drug, called tetrabenazine (TBZ), is commercially distributed
as Xenazine or Nitoman and blocks the action of dopamine. TBZ
Dimebon is an orally-available small molecule that has been shown
is approved for use in several countries, but not the US, to treat
to prevent the death of brain cells in preclinical models of HD and
uncontrollable muscle movements in HD and other neurological
Alzheimer's disease, making it a novel potential treatment for
conditions.
these and other neurodegenerative diseases. Based on the clinical
and preclinical data generated, to date, Medivation believes that
In the study, the researchers used mice that were genetically
Dimebon operates by a novel mechanism of action and may exert a
engineered to carry the mutant human gene for HD, causing
neuroprotective effect in multiple areas of the CNS. Dimebon appears
symptoms and the death of brain cells similar to those seen in the
to block a new target that involves mitochondrial pores, which
disease. The study focused on the striatum, which is primarily made
are thought to play a role in the cell death that is associated with
up of medium spiny neurons that undergo widespread death in HD.
neurodegenerative diseases and the ageing process.

Page  ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News NEURODEGENERATIVE DISORDERS

Intellect reports positive safety data from Phase Ia sclerosis (Lou Gehrig's disease), is not invalid on the grounds of
Oxigon trial anticipation. This decision comes following a remand from the Court
of Appeals for the Federal Circuit in November 2006, in which the
Intellect Neurosciences has obtained validated data and an audited Court had vacated an earlier decision of patent validity and remanded
report describing the results of a Phase Ia trial of Oxigon, which for further findings relating to a specific validity issue of anticipation
indicate no serious adverse effects in any of the subjects throughout by a prior art patent.
the dose levels.
Impax Laboratories' ANDA for its generic version of Rilutek 50mg
This double-blind, randomised, placebo-controlled, single escalating- tablets was approved on 29th January 2003 by the FDA, but the
dose study in 54 elderly healthy volunteers was conducted in product has never been sold due to an injunction entered in this
the Netherlands under Ethics Committee approval in Utrecht. patent litigation.
Intellect designed the trial to determine the safety, tolerability and
pharmacokinetics of Oxigon with and without food interactions.
Agreement News
Oxigon is a chemically-synthesised form of a small, naturally-occurring
molecule that has unique antifibrillogenic, neuroprotectant and Biogen Idec to exercise first milestone investment in
antioxidant properties. Oxigon can reduce the accumulation of ALS collaboration with Amorfix
toxic soluble amyloid beta peptides and inhibit plaque deposition.
Simultaneously, it acts as a neuroprotectant, preventing neuronal Amorfix Life Sciences has received notice from Biogen Idec that it will
damage from amyloid beta-induced oxidative stress. Preclinical be exercising the first milestone investment under an August 2006
studies using transgenic mouse models have provided evidence that research and investment agreement.
the compound has the potential to reduce brain amyloid burden
and improve cognition in Alzheimer's disease, while additional
The milestone investment allows Biogen Idec to retain its exclusive
studies have demonstrated its potential utility to treat indications
worldwide option to license Amorfix' therapeutic candidates for
and conditions such as Parkinson's, Huntington's and other diseases
amyotrophic lateral sclerosis (ALS; Lou Gehrig's disease). Biogen Idec
in which oxidative stress is believed to be a significant contributing
factor. 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
Intellect is the exclusive licensee of patents related to the use of a four-month hold period.
Oxigon, which are owned jointly by New York University and the
University of South Alabama. Patents have been granted in Europe, The companies entered into the agreement to develop and
the US and several other countries. 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
Product News the first of three predefined milestones for its therapeutic ALS
programme with Biogen Idec, the research is focused on the role
Neurochem receives second FDA approvable letter of monoclonal antibodies (Abs) targeted to misfolded superoxide
for Kiacta in AA amyloidosis dismutase-1 (SOD1) for the treatment of ALS.

Neurochem has received a second approvable letter from the FDA for Amorfix has demonstrated that a targeted immunotherapy approach
Kiacta (eprodisate), for the treatment of amyloid A (AA) amyloidosis. can diminish the motor neuron effects of ALS in animals. Its approach
is based on the premise that the misfolding and aggregation of
In its action letter, the FDA indicated that the Phase II/III trial provided SOD1 is a principal agent in the death of motor neurons in all types
some evidence of the effectiveness of Kiacta, which has received of ALS disease. Amorfix believes that if the misfolded SOD1 could be
orphan drug status in the US, EU and Switzerland, for the treatment specifically recognised and neutralised by Abs prior to aggregation,
of the renal manifestations of amyloidosis, however, the Agency also the disease could be effectively treated. This approach could be
indicated that an additional efficacy trial with a target p-value of 0.05 extended beyond ALS to other misfolded protein diseases, such as
will be necessary before it could approve the investigational product Alzheimer's and Parkinson's, where misfolded proteins have been
candidate. identified.

Furthermore, the approvable letter stated that additional submissions, Tikvah/Academia Sinica enter licensing agreement for
filed by Neurochem as part of its complete response to this neurodegenerative disorders
approvable letter, may address issues raised in this letter. The FDA
has indicated that such additional submissions could persuade it Tikvah Therapeutics has entered into an exclusive licensing agreement
to eliminate the requirement for an additional trial. The Agency also for a number of patent and patent applications with Academia Sinica
asked for additional information, including further pharmacokinetic encompassing the diagnosis, methods of use and treatments of a
studies, and again acknowledged that a QT clinical study should be variety of neurodegenerative disorders, including, amongst others,
submitted as part of a Phase IV commitment. The company expects to spinal muscular atrophy (SMA). The subject of this agreement is
file a complete response to this approvable letter in the near future. technology developed at Academia Sinica.

Rilutek patent ruled not invalid Under the terms agreed, Tikvah will be conducting the clinical
development of agents. Tikvah will pay a licensing fee, potential
The US District Court for the District of Delaware has ruled that Aventis milestones and royalty payments in exchange for an exclusive licence
Pharmaceutical's (sanofi-aventis) Patent No. 5,527,814 related to to pursue the commercial development of the technology for the
the use of Rilutek (riluzole) for the treatment of amyotrophic lateral treatment of SMA and other neurodegenerative diseases.

2nd August 2007 ©


Espicom Business Intelligence Page 
CEREBROVASCULAR DISORDERS / ANXIOLYTICS/SLEEP DISORDERS CNS Drug News

Cerebrovascular Disorders
significant difference between AX200- and placebo-treated patients
R&D Update could not be observed in the overall consideration of the usual clinical
endpoints. However, a detailed statistical evaluation of the data
SYGNIS completes Phase IIa study of AX200 in stroke provided has suggested that certain stroke patients may benefit from
a treatment with AX200.
SYGNIS Pharma has successfully completed a multi-centre, double-
blind, placebo-controlled, dose-escalation, Phase IIa study of AX200 Besides stroke, SYGNIS is currently preclinically testing the
in stroke. A comprehensive analysis of the AXIS study data show that endogenous protein, AX200, in further neurodegenerative indications,
the primary and secondary endpoints were achieved and that the such as amyotrophic lateral sclerosis (Lou Gehrig's disease).
use of AX200 in stroke patients can be considered safe. Although the
focus of the study was the collection of data regarding safety and Following the positive results of the AXIS study, SYGNIS is in the
tolerability, data on the efficacy of AX200 were also monitored. Due process of designing and preparing a Phase IIb trial, the aim of which
to the small number of patients involved in such a safety study, a will be to demonstrate the efficacy of AX200 in stroke patients.

Anxiolytics/Sleep Disorders
Severe trauma may affect children's brain function
R&D Update
The first study to examine brain activity patterns in severely-
deCODE discovery points to new RLS treatment traumatised children has suggested that their brains function
approach differently than those of healthy children, according to researchers
at the Stanford University School of Medicine and Lucile Packard
Scientists at deCODE genetics, in collaboration with colleagues from Children's Hospital.
Emory University, have discovered the first variant in the sequence of
the human genome ever linked to risk of restless legs syndrome (RLS) The study, which was published in the 27th June online edition of
and periodic limb movements (PLMs). Depression and Anxiety (10.1002/da.20346), hints at the biological
underpinnings of post-traumatic stress disorder (PTSD), as well as
The SNP in the BTBD9 gene on chromosome 6 was associated in provides a valuable benchmark with which to assess the effectiveness
Icelandic and US cohorts with an increased risk of RLS with PLMs of of potential therapies. However, it is not yet clear whether the brain
70 to 80 per cent for those who carry one copy, compared to those differences are caused by the interpersonal trauma experienced by
without the variant. It is believed to account for approximately 50 per the children or if pre-existing differences make some children more
cent of cases and was shown to associate with decreased stores of iron susceptible to developing PTSD after traumatic events than their more
in the body. resilient peers.

The discovery, which was published in the 18th July online edition of The researchers used functional MRI (fMRI) to compare brain
the NEJM (10.1056/NEJMoa072743), provides new evidence that RLS is activation patterns in 16 children with symptoms of PTSD to the
a genuine disease with an identifiable biological basis. deCODE plans patterns seen in 14 age- and gender-matched non-traumatised
to analyse the BTBD9 pathway to begin a drug-discovery programme children as they performed a simple decision-making task. It was
targeting the underlying causes of disease. found that although the two groups accomplished the task equally
well, they used different parts of their brains to do so. The children
The deCODE team analysed more than 300,000 SNPs in a total of with PTSD symptoms showed less activity than their non-traumatised
1,000 Icelandic RLS patients and controls, leading to the identification peers in the left middle frontal cortex, an area known to be involved
of a single SNP on chromosome 6p21. The strongest association was in response inhibition, and more activity in several other areas of the
between allele A of SNP rs3923809 and the combined phenotype of brain, including the insula.
RLS with PLMs.
People with PTSD often have trouble paying attention and responding
The rs3923809 is located within the BTBD gene, which is widely appropriately to experimental tasks, perhaps due to heightened
expressed in the brain and other organs. The finding was subsequently physiological arousal arising from their traumatic experience. As
confirmed in a case-control cohort from the Emory Healthcare a result, many children with PTSD symptoms are diagnosed with
Program in Sleep in Atlanta, GA. attention deficit hyperactivity disorder, but it is difficult to tell whether
the two disorders are truly related, or if they simply have overlapping
The variant identified also confers risk of PLMs without RLS, with symptoms; functional imaging such as fMRI may allow researchers to
individuals carrying two copies of the at-risk variant having two-fold solve this mystery, plus it may help doctors to devise better therapies.
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 According to lead author, Dr Victor Carrion, it may be possible to
indicator of iron stores in the body, showed that serum ferritin was 13 redirect the brain's altered processing functions. Ideally, people
per cent lower per copy of the variant carried compared to controls. will one day be able to compare brain images from before and after
Hence, this discovery supports an old notion that the pathogenesis of treatment to determine what does or does not work for children with
RLS may involve iron metabolism. PTSD.

Page 10 ©
Espicom Business Intelligence 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 CNS Drug News

Antidepressants
For details of further NNR research and a collaboration by Targacept,
R&D Update see Neurodegenerative Disorders, Alzheimer's Disease - R&D Update;
General Development News, R&D Update; and General Development
Add-on mecamylamine treatment shows positive News, Agreement News.
effects in depression

At the Summer Meeting of the British Association for Product News


Psychopharmacology (BAP), held from 22nd to 25th July, in Harrogate,
the UK, Targacept presented positive research findings suggesting that Abilify sNDA granted priority review by FDA
an add-on treatment of mecamylamine, a broad-spectrum nicotinic
antagonist, improved symptoms of depression in patients who were The FDA has accepted for filing and granted a priority review of the
inadequate responders to first-line citalopram therapy. 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
The study included an open-label citalopram phase and a subsequent
therapy (ADT). The application is based on data from two six-week,
double-blind, placebo-controlled phase in which the effects of
double-blind, randomised, placebo-controlled, multi-centre trials
mecamylamine taken with citalopram, a treatment combination
(n=743) evaluating the use of adjunctive Abilify in adult patients with
known as Tridmac, were evaluated in patients who did not respond a primary diagnosis of MDD who had an inadequate response to
adequately to citalopram alone. In the trial, the treatment combination monotherapy with one or more ADTs.
of mecamylamine and citalopram was generally well tolerated. Also,
patients showed greater improvement on symptoms of depression Biovail receives non-approval letter from FDA for
and irritability when augmented with mecamylamine, as compared
BVF-033
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
Biovail has received a non-approval letter from the FDA for its NDA
screened, 450 entered the trial and 192 were randomised to double- for BVF-033, a novel, once-daily salt formulation of bupropion for the
blind medication. Mecamylamine represents a new class of promising treatment of depression. The main issue raised by the Agency in its
antidepressant medications that target the brain's neuronal nicotinic letter related to the design of the pharmacokinetic studies required to
receptors (NNRs). Targacept's depression programme also includes support the NDA.
TC-5214, one of the enantiomers of mecamylamine hydrochloride
and a preclinical product candidate as an augmentation therapy, and Biovail believes that the studies were appropriate, but is evaluating
TC-2216, a product candidate as a monotherapy for depression and the issue and will meet with the FDA as soon as possible to discuss the
anxiety disorders that is currently in an ongoing Phase I trial. necessary steps to resolve this matter.

Psychotic Disorders
occupancy that supports the 32mg dose as being able to achieve
R&D Update clinically-efficacious dopamine blockade. The efficacy of BL-1020 was
also demonstrated by measuring the elevation in prolactin levels, an
BL-1020 shows antipsychotic efficacy; enters Phase II accepted marker for dopamine activity. There was a dose-dependent
trial in schizophrenia change in prolactin level at four hours post-dosing, further validating
earlier Phase I results. Safety and tolerability data show that there have
BioLineRx has successfully completed a study determining the clinical been no significant changes in ECG, vital signs or physical examination,
binding properties of BL-1020 to dopamine receptors in the brain. The clinical chemistry or haematology values.
study has shown that BL-1020, an orally-available, GABA-enhanced
antipsychotic clinical candidate for the treatment of schizophrenia, In addition...
blocks dopamine receptors in the human brain, providing direct
evidence of antipsychotic efficacy. The study further supports the BioLineRx has initiated a Phase II trial to determine the maximal
safety of BL-1020, as well as provides evidence that 32mg will be tolerated dose of BL-1020 in 60 patients with schizophrenia or schizo-
clinically efficacious and that the compound can be given once daily. affective disorder. This open-label, multi-centre, six-week, sequential
cohort study is expected to be conducted at five centres in Israel
The study's primary objective was to investigate the receptor and 12 centres in Romania. The dose ranges are based on results in
occupancy of BL-1020 in the human brain, however additional safety, previous studies performed on healthy volunteers.
tolerability and pharmacokinetic data were also generated. The study
was conducted in Uppsala, Sweden, and designed as a single-centre, BL-1020 is being developed by BioLineRx under a worldwide exclusive
randomised, open-label evaluation performed on three cohorts, licence from Ramot at Tel Aviv University and Bar-Ilan Research &
each with four healthy male subjects (aged 21 to 35 years) receiving Development, the technology transfer arms of Tel Aviv University
a single dose of BL-1020 16, 24 or 32mg. Receptor occupancy was and Bar-Ilan University, respectively. Data from preclinical and Phase
assessed using PET scans at 1.5, six or 24 hours post-dosing. The I studies demonstrated that the compound may retain the efficacy
PET data demonstrated a dose-dependent increase in dopamine of currently-available typical and atypical antipsychotic drugs, while

Page 12 ©
Espicom Business Intelligence 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.
Hyperactivity Disorder (MTA). Initial advantages of medication Alternatively call our
management alone or in combination with behavioural treatment UK office on tel: +44 (0) 1243 533322
over purely behavioural or routine community care waned in the US office on tel: +1 609 951 2227
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 :
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.
what the future ANTICANCER PRODUCTS Progressive grey matter loss discovered in BPD
holds • Abegrin
MedImmune
• ACA 125 Researchers at the University of Edinburgh have found that people
After years of anticipation Cell Control Biomedical with bipolar disorder (BPD) suffer from an accelerated shrinking of
and encouraging responses • adecatumumab their brain. The study shows for the first time that BPD is associated
Micromet/Merck KGaA
to pathfinder products, • Antibody 3F8
with a reduction in brain tissue and proves that the changes get
monoclonal antibodies are MSKCC progressively worse with each relapse.
now set to realise their true • BB-10901
clinical and commercial ImmunoGen Furthermore, the findings, which were published in the 9th July online
potential. But what are the •Virexx BrevaRex edition of Biological Psychiatry (10.1016/j.biopsych.2007.03.005), show
prospects for the products • catumaxomab that the loss of grey matter tissue is concentrated in areas of the brain
that control memory, face recognition and co-ordination, namely the
that will lead the market? Fresius Biotech/TRION Pharma
hippocampus, fusiform gyrus and cerebellum, respectively.
• CNT0328
Centocor
HUGE POTENTIAL • Cotara According to lead researcher, Dr Andrew McIntosh, this discovery
While large pharma companies Peregrine Pharma has implications for the way the disease is researched and may also
predictably take aim at the largest • daclizumab impact the way it is treated. The amount of brain tissue that is lost is
treatable populations (breast cancer, PDL BioPharma/Roche
greater in people with multiple episodes of illness and is associated
colorectal disease, NHL, leukaemia), • epratuzumab
Immunomedics with a decline in some areas of mental ability. However, McIntosh
there is an abundance of niches
• ertumaxomab believes another possibility is that the brain changes are caused by
for monoclonal antibody therapy
Fresius Biotech/TRION Pharma stress or genetic factors, which tend to lead both to more frequent
applications and a staggering • galiximab
number of potential disease targets. Biogen Idec illness episodes and to greater brain loss, thus further research will be
Smaller developer companies required.
• HA20/IMMV-106
are likely to become more visible Immunomedics
as their products move closer to • HuMax-EGFr
regulatory approval. Genmab
• ipilimumab
Product News
Bristol-Myers Squibb EMEA recommends authorisation of first generic
That is why this new management • KW-2871
report, published in April 2007 is Kyowa Pharmaceutical medicine for human use
essential for everyone working in • matuzumab
the field. The report covers over EMD Pharma/Merck/Takeda The EMEA has adopted a positive opinion recommending, for the
30 leading compounds originating • MDX-060 first time, the granting of a marketing authorisation for a generic of a
from the largest blue-chip Medarex centrally-authorised medicine for human use. The recommendation
multinationals to smaller developer • ofatumumab was made by the Agency's CHMP at its July meeting.
Genmab
companies. • oregovomab
Unither This first positive opinion is for Zalasta (olanzapine), from Krka, which is
KEY EVALUATION FOR EACH • Rencarex intended for the treatment of schizophrenia and moderate-to-severe
PRODUCT Wilex Centocor manic episode. The reference product for Zalasta is Eli Lilly's Zyprexa
It is vital that new compounds can • SGN-30 (olanzapine), which has been authorised in the EU since 1996. The
Seattle Genetics CHMP recommendation will now be forwarded to the EC for adoption
be seen in the wider competitive/ • ticilimumab
development landscape. For that of a decision.
Pfizer/Amgen
reason we have established a • volociximab
unique competitor analysis based PDL BioPharma Shire's Vyvanse available in US pharmacies
on each of the following criteria: • zanolimumab
Genmab/Merck KGaA Shire's Vyvanse (lisdexamfetamine dimesylate), a new once-daily
• Novelty/rationale for mechanism
of action medication approved to treat the symptoms of attention deficit
RHEUMATOLOGY
• Proof of concept/clinical data PRODUCTS hyperactivity disorder (ADHD), is now available in US pharmacies
• Management/clinical expertise • belimumab nationwide. The FDA approved Vyvanse on 23rd February and the
• Competition within the Human Genome Sciences/GSK product is now available in retail pharmacies in 30, 50 and 70mg
marketplace • certolizumab pegol dosage strengths.
• Risks associated with developing a UCB
• golimumab Vyvanse works with the patient's natural metabolism to deliver active
drug within a therapeutic class Centocor/Schering Plough
medication and significantly improves core ADHD symptoms of
• HuMax CD-20
Order your copy today Genmab inattention and behaviour. In a randomised, double-blind, placebo-
• tocilizumab controlled, Phase III study, all three doses of the drug demonstrated
www.espicom.com/mab Chugai/Roche significant improvements in ADHD Rating Scale-IV scores compared

Page 14 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News ANALGESICS/ANAESTHETICS

with placebo (p<0.0001) after four weeks of once-daily treatment. The Parent Rating Scale. The most common side effects reported in this
effects were maintained throughout the day based on parent ratings study were decreased appetite, difficulty falling asleep, stomach ache
reported at approximately 10am, 2pm and 6pm using the Connors' and irritability.

Analgesics/Anaesthetics
Posidur 5mL treatment group versus placebo (p=0.0007). A total
R&D Update of 53 per cent of the study patients in the Posidur 5mL group took
supplemental opioid analgesic medications versus 72 per cent of the
Study may accelerate research into next generation of placebo patients (p=0.0909). During the periods of one to 24 hours,
painkillers 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-
Scientists studying amoeboid organisms commonly known as slime times (p=0.0172) more supplemental opioid analgesic medications,
moulds have helped to unravel the structure of a key molecule that respectively, than the Posidur 5mL treatment group. In addition, the
controls pain in humans. It is thought that the findings, published in median time to first use of supplemental opioid analgesic medication
the 12th July issue of Nature (2007;448:200-203), could rapidly advance after surgery for the placebo patients was 2.7 hours versus >72 hours
research into the next generation of painkillers for the relief of chronic for the Posidur 5mL treatment group (p=0.0197).
conditions, such as migraine and backache.
The patient groups treated with Posidur showed comparable safety
Chronic pain has no apparent physiological benefit, often being profiles to those treated with placebo and the drug administration
referred to as the ''disease of pain.'' Complete and lasting relief of appeared to be well tolerated. Additionally, the side effects commonly
chronic pain is rare and often, the clinical goal is pain management observed with opioid medication use were less frequent in the Posidur
through one or more medications. But now, researchers at the treatment groups compared to placebo.
University of Manchester have examined the microscopic amoeboid
organisms in a bid to gain greater insight into pain molecules known Durect has scheduled an end-of-Phase II meeting with the FDA in
as P2X receptors. preparation for the Phase III programme, for which it intends to select
Posidur 5mL, as this dose showed statistically significant activity
In humans, P2X receptors look identical to one another, therefore relative to placebo, whereas Posidur 2.5mL showed a positive trend
scientists have had difficulty understanding how they function. The relative to placebo on certain parameters, but the results were not
researchers discovered that there was only a 10 per cent similarity statistically significant.
between human P2X and the slime mould equivalent, and were
therefore able to deduce from evolutionary theory that it was these The decision for advancing Posidur into Phase III trials was based
similar parts of the molecule that probably regulate pain in humans. on this study and the successful results trigger an US$8 million
milestone payment from Nycomed to Durect under the parties'
This is thought to be a big step forward in understanding how the collaborative agreement. Durect has licensed Nycomed the exclusive
molecule works and should make it possible to develop drugs that commercialisation rights to Posidur in the EU and select other
block the receptors' actions. Inhibiting P2X as a potential pain-relief countries, plus will manufacture and supply the product to Nycomed.
therapy could revolutionise the way that chronic pain conditions are The company may earn additional milestone payments of up to
managed. US$180 million, due upon the achievement of additional defined
development, regulatory and sales milestones, in addition to blended
Durect reports positive Phase IIb Posidur data royalties.

Durect has also been conducting smaller exploratory Phase II studies


Durect has reported positive results from a 122-patient, Phase IIb trial
in hernia, shoulder arthroscopy and appendectomy surgeries to
of Posidur (SABER-bupivacaine) for the treatment of postoperative
evaluate different application techniques, clinical design and conduct,
pain in patients undergoing inguinal hernia repair, where the long-
as well as other investigational factors. In all of the exploratory studies,
acting local anaesthetic demonstrated statistically significant
patient groups treated with Posidur showed comparable safety
reductions in pain and total consumption of supplemental opioid
profiles as the placebo groups and the drug administration appeared
analgesic medications versus placebo.
well tolerated. Some treatment groups from the hernia and shoulder
exploratory studies utilising Posidur have shown positive activity as
The multi-centre, double-blind, placebo-controlled study was
measured by a reduction of pain or the consumption of supplemental
conducted in Australia and New Zealand, and designed to evaluate the
opioid analgesic medication versus placebo, while other treatment
tolerability, activity, dose response and pharmacokinetics of Posidur
groups have not.
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). Newron reveals additional analyses of ralfinamide
Phase II study
In relation to the co-primary endpoint of pain reduction, as measured
by Mean Pain Intensity on Movement area under the curve (AUC) Newron Pharmaceuticals has reported further results from the first
one to 72 hours post-surgery, the patient group treated with Posidur placebo-controlled, randomised treatment trial of ralfinamide in
5mL reported 31 per cent less pain versus placebo (p=0.0033), patients with various types of neuropathic pain, including diabetic
plus a 35 per cent reduction of pain as measured by Mean Pain neuropathy. Previously-announced results indicated the statistically
Intensity on Movement AUC for the period one to 48 hours post- significant superiority (p=0.019; 95% CI -14.9, -1.4) of ralfinamide
surgery, a secondary endpoint measure, was reported between the compared with placebo on the patient-rated Visual Analogue Scale

2nd August 2007 ©


Espicom Business Intelligence Page 15
ANALGESICS/ANAESTHETICS CNS Drug News
(VAS), while showing good tolerability at the doses tested (see CNS Organon's MAA for sugammadex accepted for review
165). Additional analyses have revealed that ralfinamide treatment
is associated with multiple statistically significant differences and Organon's (Akzo Nobel) MAA for sugammadex has been accepted
clinically-relevant benefit over placebo, as judged by: for review by the EMEA. This novel selective relaxant-binding agent
is specifically designed to reverse the effects of the muscle relaxant,
• responder analysis using multiple definitions of the magnitude of rocuronium bromide (Esmeron/Zemuron), used as part of general
pain relief, as judged on the VAS (overall p<0.05); anaesthesia during surgical procedures.
• significant improvement in the mean ratings of the patient-rated
Daily Pain Diary (p=0.003; 95% CI -1.5, -0.3); The MAA is based on safety and efficacy data from over 1,700 patients,
• significant improvement in the quality of sleep, as judged by the including data from ten global Phase III trials. The results of four of
patient (p=0.002; 95% CI -1.5, -0.4); and these studies were presented at the 14th Annual Euroanaesthesia
• significant improvement in daily activities (p=0.033; 95% CI -1.4, 2007 Congress in June (see CNS 164).
-0.1).
Sugammadex works by encapsulating the muscle relaxant molecule
Meda agrees to acquire MedPointe and forming a tight complex. The encapsulation of the muscle relaxant
by sugammadex removes the drug from its site of action and renders
Meda AB has agreed to acquire MedPointe for US$520 million in cash it inactive. In clinical trials conducted, to date, sugammadex has
and 17.5 million newly-issued Meda shares. With approximately 710 generally demonstrated the ability to reverse shallow and profound
employees and headquartered in Somerset, NJ, MedPointe is focused depths of rocuronium-induced neuromuscular blockade within three
on two of Meda's priority areas, pain and allergy/respiratory. minutes, thereby enabling control of the onset and offset of skeletal
muscle relaxation through the use of both drugs. Sugammadex has
With the acquisition, Meda will have full marketing coverage in both also demonstrated the ability to reverse the effects of vecuronium-
the US and Europe, with revenues approaching US$1.4 billion, and induced (Norcuron) neuromuscular blockade. Sugammadex' global
the acquisition is expected to be accretive to Meda's EPS, at the latest, Phase III development programme, consisting of five US and five
during 2009. European trials, completed recruitment in late 2006. The anticipated
submissions for the US and Japan are proceeding in line with the
Akela completes enrolment in Phase IIb trial of previously-disclosed timelines.
Fentanyl TAIFUN
RxElite launches generic sevoflurane in the US
Akela Pharma (formerly LAB International) has completed patient
enrolment in its Phase IIb trial of Fentanyl TAIFUN, a fast-acting RxElite Holdings (Southridge Technology) has launched Sojourn
fentanyl formulation that is delivered using the company's TAIFUN dry (sevoflurane), a generic inhalation anaesthetic, in the US. The company
powder inhaler platform. is Minrad International's exclusive commercial partner for the product
in this market, where it received FDA approval on 2nd May. RxElite
This is a multi-centre, multi-national trial in cancer patients with severe currently markets three anaesthetic gases in the partnership with
persistent pain on maintenance opioid therapy. The first part of the Minrad: sevoflurane, isoflurane and enflurane. RxElite is the third
trial is a single-arm, open-label dose titration to evaluate the effective entrant into the US sevoflurane market, following Abbott (with Ultane)
individual dose for significant pain relief with Fentanyl TAIFUN in the and Baxter.
treatment of breakthrough cancer pain.
US PTO allows Opana ER-related patent application
The second part includes 28 responders from the open-label arm who
are randomised to receive the titrated doses or placebo. It is expected The US PTO has indicated that Penwest Pharmaceuticals' patent
that safety and efficacy data from this double-blind, placebo- application claiming the sustained-release formulation of
controlled extension arm will be available by early September. 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
Product News rejection, the company amended the claims and the PTO examiner
found these allowable.
Ortho-McNeil/Par settle Ultracet patent litigation
Opana ER, which is marketed by Endo Pharmaceuticals, uses Penwest's
TIMERx technology and is indicated for the treatment of moderate-to-
Ortho-McNeil Pharmaceutical (Johnson & Johnson) has settled patent
severe pain in patients requiring continuous, around-the-clock opioid
litigation against the generic drug manufacturer, Par Pharmaceutical
treatment for an extended period of time. The patent, once issued, will
Companies, and its subsidiaries, Par Pharmaceutical and Kali
be scheduled to expire in 2022 and Penwest expects that Endo will list
Laboratories, regarding their infringement of the patent for Ultracet
this patent at the earliest opportunity in the FDA's Orange Book.
(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.
Agreement News
As part of the settlement, Par/Kali acknowledged that the re-issue
patent for Ultracet is valid and enforceable, and that they infringed it Hydra signs global TRPV3 collaboration with Pfizer
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 Hydra Biosciences has signed a collaboration agreement with Pfizer
a royalty-bearing licence until their product's agreed-upon exit from Global Research & Development that will be focused on TRPV3
the market on 15th November 2007. antagonist product candidates for pain. The transient receptor

Page 16 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News THERAPIES TO TREAT SUBSTANCE DEPENDENCE / ANTI-EPILEPTICS

potential (TRP) channel family comprises a novel group of non- newly-acquired rights provide Tikvah with claims encompassing the
selective cation channels that are distinct from classical voltage- chronic treatment of pain and pain-related indications with glycine
gated ion channels. Under the terms agreed, Hydra will receive up- receptor agonists as monotherapy or in combination with certain
front and success-based development milestone payments totalling other agents.
US$195 million for the first developed product launched, with upside
potential for additional approved indications. Furthermore, there The subject of this agreement is technology developed by researchers
are opportunities for the development of additional products. Pfizer at Northwestern University in the area of pain and perception. This
will fund all research and development under the agreement, plus work has suggested that treatment with certain classes of glycine
receive exclusive access to Hydra's current TRPV3 patents, as well receptor agonists, alone or in combination with other agents, can
as an exclusive licence to commercialise any compound from the be used to treat chronic pain, as well as modify the structural brain
collaboration. Once the products are on the market, Pfizer will pay changes that occur under conditions of chronic pain.
worldwide royalties to Hydra.
The studies of various brain processes in humans and animals
Tikvah enters licensing agreement with Apkarian using non-invasive brain imaging techniques, coupled with brain
electrophysiology and knowledge of neural networks, afford a
Tikvah Therapeutics has entered into an exclusive licensing agreement differentiated approach to understanding the perception of touch
with Apkarian Technologies for patents and patent applications and pain.
involving certain agonists of specific sites of the NMDA receptor. These

Therapies to Treat Substance Dependence


Editor's note: NicVAX is Nabi's innovative and proprietary
R&D Update investigational vaccine that is being developed to treat nicotine
addiction and prevent smoking relapse.
Nabi creates pharmaceuticals business unit
Drug may help people with OCD; to be tested on
Nabi Biopharmaceuticals has created the second of its two smokers
planned strategic business units, Nabi Pharmaceuticals, which will
be responsible for the NicVAX (nicotine conjugate vaccine) and For details, see Psychotic Disorders, R&D Update.
StaphVAX (Staphylococcus aureus polysaccharide conjugate vaccine)
development programmes, as well as the continuing milestone-
related development obligations following the sale of PhosLo (calcium Product News
acetate).
UK's NICE issues guidance on Champix for smoking
The company announced in June that it had created the Nabi Biologics cessation
units, as well as a Corporate Shared Services group to support these
business units. The UK's National Institute for Health and Clinical Excellence (NICE)
has issued guidance recommending Pfizer's Champix (varenicline) as
In connection with the reorganisation required to support the an effective treatment for helping smokers to quit. The drug, within
business strategy of this latest unit, the company eliminated 33 its licensed indications, is recommended as an option for smokers
positions in its Rockville, MD, research and development facility. This who have expressed a desire to quit smoking, but should normally be
reduction of approximately 5 per cent of the company's total current prescribed only as part of a programme of behavioural support. These
recommendations are part of a suite of guidance being produced by
workforce is expected to yield approximately US$3.3 million in savings
NICE on the most effective methods of tackling smoking and what
on an annualised basis.
works to help people quit.

Anti-Epileptics
efficacy for the treatment of partial seizures, generalised seizures and
R&D Update treatment-resistant seizures. In addition, ICA-105665 has also been
shown to have activity in models of neuropathic and inflammatory
Icagen files IND for novel epilepsy compound pain.

Icagen has filed an IND application with the FDA for ICA-105665, a ICA-105665 will be administered orally and is intended to be
novel small-molecule compound for the treatment of epilepsy. developed as a chronic therapy for patients with epilepsy.
Provided that the IND is accepted, Icagen plans to initiate a Phase
ICA-105665 is an activator of subtypes of KCNQ ion channels, which I trial during the third quarter of 2007; this will be a double-blind,
are attractive targets for the treatment of epilepsy based on their placebo-controlled study conducted in healthy male volunteers
function and genetic linkage to a seizure disorder. In preclinical to assess the safety, tolerability and pharmacokinetics of the
studies, ICA-105665 was active in animal models predictive of compound.

2nd August 2007 ©


Espicom Business Intelligence 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

information. The CHMP has now recommended upgrading this


Product News warning, suggesting that treatment with Acomplia should be stopped
if a patient develops depression, as well as the inclusion of additional
CHMP recommends upgraded warnings for Acomplia information on the psychiatric safety of the drug.

Following an assessment of the information on psychiatric adverse Acomplia's labelling has been updated based on data reflecting a year
events associated with sanofi-aventis' first-in-class CB1 blocker, of post-marketing experience, mainly from Germany, France and the
Acomplia (rimonabant), the EMEA's CHMP has recommended UK, as well as the results of five additional clinical trials completed
the addition of a contraindication in patients with ongoing major since the original dossier was approved.
depression or who are being treated with antidepressants, because
of the risk of psychiatric side effects. Finalising its assessment of the Editor's note: earlier in July, sanofi-aventis decided to withdraw the
available data at its 16th to 19th July meeting, the CHMP did, however, NDA for rimonabant in the US, where it is branded Zimulti, following
conclude that except in these patients, the benefits of Acomplia a decision by the FDA's Endocrinologic and Metabolic Drugs Advisory
continue to outweigh its risks. Committee to not recommend the product's approval. Additionally, in
February 2006, the company received a non-approvable letter from
Acomplia has been authorised in the EU since June 2006 and is the FDA's Division of Metabolism and Endocrinology Products for
marketed in 13 European countries as an adjunct to diet and exercise smoking cessation and in May that year, the CHMP adopted a negative
for the treatment of obese or overweight adult patients. Psychiatric opinion for Acomplia for this indication. This most recent decision
side effects, in particular depression, were identified as the main safety for rimonabant in obesity is unlikely to improve its chances as an
issue at the time of approval and reflected in the medicine's product approved smoking cessation product.

Drugs used in Nausea & Vertigo


Ethypharm will pursue registration of ondansetron Flashtab in China, a
Agreement News process that is expected to be completed in 2009. Beijing Med-Pharm
will then be responsible for sales, marketing, distribution and supply.
Shanghai Ethypharm signs ondansetron licence
agreement with Beijing Med-Pharm Ondansetron is a member of the 5-HT3 antagonist class of anti-emetics
and marketed under the tradename, Zofran, by GlaxoSmithKline.
Shanghai Ethypharm Pharmaceutical (Ethypharm) has signed an The drug is indicated to reduce nausea and vomiting (N&V) induced
exclusive licence agreement under which Beijing Med-Pharm will by cytotoxic chemotherapy and radiotherapy, as well as prevent
market and distribute ondansetron Flashtab (4 and 8mg) in China once postoperative N&V. Ethypharm manufactures the product using its
the drug is approved in this market. Under the terms agreed, Shanghai proprietary Flashtab orally-disintegrating tablet technology.

General Development News


intensity for 30 minutes after electrical jolts ceased. These slow signals
R&D Update are produced by a nerve cell receptor called mGluR1, which has been
associated with addiction and epilepsy. Both of these conditions also
Study further links addiction and memory involve long-term changes in the function of nerve connections,
therefore in addition to furthering the basic understanding of
People's experiences can trigger long-term changes in the strength memory storage, Linden believes the team's work suggests that drugs
of connections between nerve cells in the brain and these persistent designed to alter mGluR1 are promising candidates for the treatment
changes are how the brain encodes information as memory. Now, of addiction, epilepsy and diseases of memory.
Johns Hopkins researchers have discovered a new biochemical
mechanism for memory storage, one that may have a connection with Targacept/Abbott initiate Phase I trials of NNR
addictive behaviour. modulators

Previously, the long-term changes in connection were thought to Targacept has initiated a Phase I trial of TC-5619, a novel small molecule
only involve a fast form of electrical signalling in the brain, however that modulates the activity of the neuronal nicotinic receptor (NNR)
neuroscience professor, Dr David Linden, and his colleagues have subtype, alpha7. The double-blind, placebo-controlled study is
shown that another, much slower form of electrical signalling designed to evaluate the safety, tolerability and pharmacokinetics of
lasting approximately a second, can also be persistently changed by TC-5619, with single escalating doses administered orally to healthy
experience. volunteers.

The researchers, whose work was published in the 19th July issue of TC-5619 was discovered using Targacept's proprietary drug design
Neuron (2007;55:277-287), simulated natural brain activity by applying technology known as Pentad and is the lead product candidate in its
short electrical jolts to slices of rat brain and measuring the current alpha7 NNR programme. The alpha7 NNR is associated with a variety
flowing across the cells. After repeated jolting, the strength of the of biological functions. In particular, it has been shown in animal
slow nerve signals had dramatically decreased and remained at a low studies to be an essential regulator of both inflammation arising from

2nd August 2007 ©


Espicom Business Intelligence Page 19
GENERAL DEVELOPMENT NEWS CNS Drug News
injury or infection and cognitive functions. Published in vitro studies commercialise Edison's drug candidate, EPI-A0001, in all fields of use.
have also suggested that the alpha7 NNR plays a role in protecting EPI-A0001 has been granted orphan drug status by the FDA for the
neuronal cells from deterioration and death, however Targacept has treatment of inherited mitochondrial respiratory chain diseases, and
not yet definitively selected the indication for which it will pursue the Penwest intends to submit an IND application and commence clinical
development of TC-5619. development of the compound in early 2008. Additionally, Penwest
has the exclusive worldwide rights to develop and commercialise one
For details of further NNR research and a collaboration by Targacept, additional drug candidate to be selected from those identified by
see Neurodegenerative Disorders, Alzheimer's Disease - R&D Update; Edison during the term of the sponsored research collaboration.
Antidepressants, R&D Update; and General Development News,
Agreement News. The financial terms of the agreement call for Penwest to provide
Edison with an up-front payment, a US$1 million loan and sponsored
In addition... 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
NeuroSearch's development and licence partner, Abbott, has enrolled discretion, extend the term of the sponsored research period by up to
and dosed the first patients in a Phase I study with the drug candidate, an additional 18 months. The agreement also provides for payments
ABT-560, which has treatment potential within a variety of CNS upon the exercise of certain options, success-based milestones
disorders. The initiation of this study releases a milestone payment to payments and royalties on net sales of any products commercialised
NeuroSearch. as a result of the collaboration.

ABT-560 is also an NNR modulator that has shown promise in Antares signs product development and licence
preclinical models relevant for the treatment of cognitive deficits. agreement with Jazz
According to the terms of the companies' licence agreement, Abbott
has all rights to ABT-560 and will finance all costs relating to the Antares Pharma has signed a worldwide product development and
development and commercialisation of the drug. NeuroSearch will licence agreement with Jazz Pharmaceuticals, which demonstrates
receive milestone payments, as well as royalties on Abbott's global the successful completion of a feasibility agreement that was initiated
sales, if the drug is successfully commercialised. 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
Agreement News transdermal delivery) system.

Corcept enters microdosing study agreement with Under the terms agreed, Jazz will pay Antares up-front and product
Xceleron development milestone payments, in addition to payments for any
future development activities. Antares will also receive royalties
Corcept Therapeutics has entered into an agreement for a human on product sales upon commercialisation, including minimum
microdosing study of one of its new chemical entities, a selective GR- royalties. Total milestone and minimum royalty payments could add
II antagonist, utilising Xceleron's accelerator mass spectrometry (AMS) up to US$16.5 million or more over the life of the agreement. Jazz
technology. GR-II antagonists have potential to be used in treating is responsible for the development and commercialisation of this
numerous neurological disorders, including early dementia (including product candidate and will cover the costs of clinical trials, regulatory
Alzheimer's disease), psychosis associated with cocaine addiction and filings, plus all manufacturing and marketing associated with the
the weight gain associated with antipsychotic medication. product.

Cortex initiated a discovery research programme to identify and GSK forms US$1.5 billion CNS pact with Targacept
patent selective GR-II antagonists to develop a pipeline of products
for proprietary use. Three distinct series of GR-II antagonists GlaxoSmithKline and Targacept have formed a strategic alliance that is
were identified that appear to be as potent as Corcept's Corlux valued at up to approximately US$1.5 billion, to discover, develop and
(mifepristone) in blocking cortisol, but unlike this product, they do market novel therapeutics that selectively target specified neuronal
not block progesterone and other steroid receptors. The company nicotinic receptors (NNRs) to treat CNS conditions such as pain,
will evaluate the compound that develops particularly high plasma smoking cessation, obesity, addiction and Parkinson's disease. GSK will
and brain concentrations in an animal model, in a human microdosing participate in the alliance through its Center of Excellence for External
study using Xceleron's AMS technology. Under the terms agreed, Drug Discovery.
Xceleron will carry out the work using ultra-sensitive AMS, which
enables human drug-metabolite profiling to be performed in the early
Under the terms agreed, GSK will make an initial up-front payment of
stages of clinical development.
US$35 million to Targacept, which includes an investment of US$15
million for the purchase of 1,275,502 shares of Targacept common
Penwest/Edison enter collaboration for neurological stock. In addition, Targacept is eligible to receive up to US$1.5 billion
disorders in payments from GSK, contingent upon the achievement of specified
discovery, development, regulatory and commercial milestones across
Penwest Pharmaceuticals has entered into a research, development, five therapeutic focus areas, as well as tiered double-digit royalties
commercialisation and licence agreement with Edison Pharmaceuticals dependent on sales achieved.
for the treatment of neurological disorders resulting from defects in
cellular energy metabolism. The alliance includes Targacept's lead product candidates for pain, TC-
2696, which is currently in a Phase II trial for acute postoperative pain,
The initial focus of the collaboration is to pursue treatments for and TC-6499, a preclinical product candidate that is currently planned
orphan diseases of the mitochondria. Under the terms agreed, for development for neuropathic pain. Targacept has retained an
Penwest has obtained exclusive worldwide rights to develop and option to co-promote the aforementioned drugs to specialists and

Page 20 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News CONFERENCE LISTINGS

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

COMPANY INDEX
Abbott........................................................................................................................16, 19, 20 Kissei Pharmaceutical.....................................................................................................6, 8
Academia Sinica.................................................................................................................... 9 Krka............................................................................................................................................14
Affiris........................................................................................................................................... 4 Lucile Packard Children’s Hospital.............................................................................10
Akela Pharma........................................................................................................................16 Meda AB..................................................................................................................................16
Akzo Nobel............................................................................................................................16 Medivation............................................................................................................................... 8
Almirall....................................................................................................................................... 7 MedPointe.............................................................................................................................16
Amorfix Life Sciences......................................................................................................... 9 Merck & Co............................................................................................................................... 6
Antares Pharma...................................................................................................................20 Merck KGaA............................................................................................................................. 3
Apkarian Technologies....................................................................................................17 Merck Serono......................................................................................................................... 3
AstraZeneca............................................................................................................................ 4 Minrad......................................................................................................................................16
Avicena Group...................................................................................................................3, 8 Nabi Biopharmaceuticals...............................................................................................17
Bar-Ilan Research & Development.............................................................................12 Neurochem.........................................................................................................................5, 9
Baxter.......................................................................................................................................16 Neuroptix................................................................................................................................. 6
Bayer........................................................................................................................................... 7 NeuroSearch.........................................................................................................................20
Beijing Med-Pharm...........................................................................................................19 New York University............................................................................................................ 9
Biogen Idec.............................................................................................................................. 9 Newron Pharmaceuticals.......................................................................................... 3, 15
BioLineRx................................................................................................................................12 Northwestern University................................................................................................17
BioMS Medical....................................................................................................................... 6 Novartis..................................................................................................................................... 5
Biovail.......................................................................................................................................12 Nuon Therapeutics..........................................................................................................6, 8
Boehringer Ingelheim........................................................................................................ 1 Nycomed................................................................................................................................15
Bristol-Myers Squibb........................................................................................................12 Orexigen Therapeutics....................................................................................................18
Cambridge Laboratories.................................................................................................. 8 Organon..................................................................................................................................16
Caraco Pharmaceutical Laboratories.......................................................................11 Ortho-McNeil Pharmaceutical.....................................................................................16
Cephalon................................................................................................................................11 Otsuka..................................................................................................................................7, 12
Children’s Hospital Boston............................................................................................... 4 Par Pharmaceutical Companies..................................................................................16
Chromos Molecular Systems.......................................................................................... 7 Penwest Pharmaceuticals...................................................................................... 16, 20
Columbia University....................................................................................................4, 13 Pfizer..................................................................................................................................16, 17
Corcept Therapeutics.......................................................................................................20 Proximagen Neuroscience.............................................................................................. 3
Cortex Pharmaceuticals.................................................................................................... 3 RxElite.......................................................................................................................................16
deCODE genetics.......................................................................................................... 1, 10 sanofi-aventis.................................................................................................................. 9, 19
Duke University.................................................................................................................1, 6 Sepracor..................................................................................................................................11
Durect......................................................................................................................................15 Shire...........................................................................................................................................14
Edison Pharmaceuticals..................................................................................................20 Southridge Technology..................................................................................................16
Eisai............................................................................................................................................11 Southwestern Medical Center....................................................................................... 8
Elan.............................................................................................................................................. 3 Stanford University............................................................................................................10
Eli Lilly.......................................................................................................................................14 Summit...............................................................................................................................3, 18
Emory University........................................................................................................... 1, 10 SYGNIS Pharma....................................................................................................................10
Endo Pharmaceuticals.....................................................................................................16 Targacept......................................................................................................4, 12, 19, 20, 21
Ethypharm.............................................................................................................................19 Tel Aviv University..............................................................................................................12
Genaera...................................................................................................................................18 Tikvah Therapeutics.................................................................................................... 9, 17
GlaxoSmithKline..........................................................................................................19, 20 University of California...................................................................................................... 6
Glenmark Pharmaceuticals............................................................................................. 7 University of Cambridge................................................................................................... 6
GW Pharmaceuticals........................................................................................................... 6 University of Edinburgh..................................................................................................14
Harvard Medical School.................................................................................................... 4 University of Manchester...............................................................................................15
Howard Hughes Medical Institute............................................................................... 4 University of Miami............................................................................................................. 6
Hydra Biosciences..............................................................................................................16 University of Minnesota..................................................................................................13
Icagen.......................................................................................................................................17 University of South Alabama.......................................................................................... 9
Impax Laboratories............................................................................................................. 9 University of St Andrews.................................................................................................. 4
Intellect Neurosciences..................................................................................................... 9 University of Texas............................................................................................................... 8
Jazz Pharmaceuticals........................................................................................................20 Vanderbilt University.......................................................................................................... 6
Johns Hopkins......................................................................................................................19 VASTox....................................................................................................................................... 3
Johnson & Johnson...........................................................................................................16 Xceleron..................................................................................................................................20
Kali Laboratories.................................................................................................................16

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Page 22 ©
Espicom Business Intelligence 2nd August 2007
CNS Drug News COMPOUND INDEX

Compound INdex
Abilify........................................................................................................................................12 rimonabant............................................................................................................................19
ABT-560...................................................................................................................................20 rivastigmine............................................................................................................................ 5
acetaminophen...................................................................................................................16 Rizaben...................................................................................................................................... 6
Acomplia.................................................................................................................................19 safinamide............................................................................................................................... 3
Affitope AD01......................................................................................................................... 4 Sativex....................................................................................................................................6, 7
AL-02........................................................................................................................................... 8 sevoflurane............................................................................................................................16
Alzhemed................................................................................................................................. 5 SMT 14400................................................................................................................................ 3
aripiprazole............................................................................................................................12 SMT C1100................................................................................................................................ 3
AX200.......................................................................................................................................10 SMT D001................................................................................................................................. 3
AZD3480................................................................................................................................... 4 SMT D002................................................................................................................................. 3
BL-1020..............................................................................................................................12, 13 SMT D003................................................................................................................................. 3
bupivacaine...........................................................................................................................15 Sojourn....................................................................................................................................16
bupropion.......................................................................................................................12, 18 StaphVAX................................................................................................................................17
BVF-033...................................................................................................................................12 sugammadex.......................................................................................................................16
calcium acetate...................................................................................................................17 TC-1734....................................................................................................................................... 4
cannabidiol.............................................................................................................................. 6 TC-2216.....................................................................................................................................12
Champix..................................................................................................................................17 TC-2696....................................................................................................................................20
CHR-1103...............................................................................................................................7, 8 TC-5214.....................................................................................................................................12
CHR-1201...............................................................................................................................7, 8 TC-5619..............................................................................................................................19, 20
citalopram..............................................................................................................................12 TC-6499....................................................................................................................................20
Corlux.......................................................................................................................................20 tetrabenazine......................................................................................................................... 8
creatine...................................................................................................................................... 3 tetrahydrocannabinol........................................................................................................ 6
CX717.......................................................................................................................................... 3 tramadol.................................................................................................................................16
D-cycloserine........................................................................................................................13 tramiprosate........................................................................................................................... 5
Dimebon................................................................................................................................... 8 tranilast..................................................................................................................................6, 8
Empatic....................................................................................................................................18 Tridmac....................................................................................................................................12
enflurane................................................................................................................................16 trodusquemine...................................................................................................................18
EPI-A0001...............................................................................................................................20 Ultane.......................................................................................................................................16
eprodisate................................................................................................................................ 9 Ultracet....................................................................................................................................16
eszopiclone...........................................................................................................................11 varenicline..............................................................................................................................17
Excalia.......................................................................................................................................18 Vyvanse...................................................................................................................................14
Exelon......................................................................................................................................... 5 Xenazine................................................................................................................................... 8
fentanyl....................................................................................................................................16 Zalasta......................................................................................................................................14
Fentanyl TAIFUN..................................................................................................................16 Zimulti......................................................................................................................................19
ICA-105665.............................................................................................................................17 Zofran.......................................................................................................................................19
isoflurane................................................................................................................................16 zonisamide............................................................................................................................18
Kiacta.......................................................................................................................................... 9 Zyprexa....................................................................................................................................14
lisdexamfetamine dimesylate.....................................................................................14
Lunesta....................................................................................................................................11
A new market-leading strategic analysis from Espicom
Lunivia......................................................................................................................................11
MBP8298................................................................................................................................... 6 EmErging OppOrtunitiEs
in inhalatiOn & nasal
mecamylamine....................................................................................................................12
mifepristone..........................................................................................................................20
Mirapex...................................................................................................................................... 1
modafinil.................................................................................................................................11 spray gEnEric Drugs
MSI-1436..................................................................................................................................18
nicotine.............................................................................................................................13, 17 From emerging specialist manufacturers to
NicVAX.....................................................................................................................................17 established companies seeking new opportunities,
Nitoman.................................................................................................................................... 8 alternative drug-delivery technologies are
olanzapine.............................................................................................................................14 increasingly being seen as a route to a competitive
ondansetron.........................................................................................................................19 edge in the generics industry.
Opana.......................................................................................................................................16 This new report from Espicom provides a complete
Oxigon....................................................................................................................................... 9 review of the emerging opportunities and operating
oxymorphone......................................................................................................................16 environment for inhalation and nasal spray drugs.
PD-02.......................................................................................................................................... 3
PhosLo......................................................................................................................................17 Providing…
Posidur.....................................................................................................................................15 • Product forecasts by value 2006 to 2011
pramipexole............................................................................................................................ 1 • Patent expiry opportunities to 2016
Provigil.....................................................................................................................................11 • Generic market context
PRX4............................................................................................................................................ 3 • Competitive evaluation with 18 company
ralfinamide......................................................................................................................15, 16 reviews
Rilutek......................................................................................................................................... 9
riluzole........................................................................................................................................ 9
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2nd August 2007 ©
Espicom Business Intelligence Page 23
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