CNS Seminar
GlaxoSmithKline PLC
23 November 2004
Issued - Tuesday 23 November 2004, London
GlaxoSmithKline Reviews Novel Therapeutics For CNS Disorders And Confirms Strong
Pipeline Momentum
Today GlaxoSmithKline plc (GSK) gave investors and financial analysts an update
on its compounds in development to treat Central Nervous System disorders, a
therapy area that represents approximately 20% of the company's total R&D
pipeline. The CNS seminar represents the first in a series of key therapy area
updates that GSK will conduct once or twice a year to provide an in-depth look
at segments of its research portfolio.
Separately, the company also issued today an updated listing of all compounds in
its clinical research pipeline, which is available on the company's website,
www.gsk.com.
CNS Therapy Area Highlights
• GSK's broad CNS research portfolio offers the opportunity to provide
significant patient benefit in a range of painful and debilitating disorders for
which current therapy is often inadequate.
- New compounds have significant potential to fight neurodegenerative and
psychiatric diseases, including the first oral integrin antagonist for multiple
sclerosis, novel treatments for Alzheimer's disease and schizophrenia, and new
mechanisms to treat depression and anxiety.
- '381, a new dual-acting Cox-2 inhibitor, shows significant efficacy in
a variety of pain models.
- Radafaxine ('162) continues in development as a treatment for
depression. Based on clinical trial results showing weight loss, GSK now also
expects to develop radafaxine for the treatment of obesity.
- Several key product launches and filings are planned for 2005-2007,
including Entereg for Post Operative Ileus; Requip/Adartrel for Restless Leg
Syndrome; Trexima, a new combination therapy for migraine; Lamictal for
schizophrenia; and Lamictal XR, an improved once-daily formulation.
• GSK's R&D pipeline productivity continues to increase:
- 148 projects in clinical development, including 90 new chemical
entities (NCEs) - an 80% increase since the merger
- 45 NCEs now in Phase II development, a 41% increase over last year
- 21 NCEs/Vaccines in Phase III/registration, including Allermist,
Boniva, Cervarix, lapatinib, Rotarix, and Vesicare.
"Within a growing research pipeline of quality compounds that cross a wide range
of disease areas, GlaxoSmithKline is building a strong stable of medicines with
significant potential to fight neurodegenerative and psychiatric diseases. With
'381, for example, we have a potential best-in-class pain medicine," said Tachi
Yamada, Chairman of R&D at GlaxoSmithKline. "Our scientists are developing a new
oral treatment for multiple sclerosis, novel treatments for Alzheimer's disease
and schizophrenia, and new ways to treat depression and anxiety. Our emerging
CNS portfolio could potentially make a huge difference to the lives of millions
of patients."
PAIN
Dual-acting Cox-2 inhibitor shows strong efficacy for the treatment of pain.
406381, a new dual-acting Cox-2 inhibitor, is active in pre-clinical models in
both inflammatory and neuropathic pain.
In Phase II studies for rheumatoid arthritis and osteoarthritis, '381 had better
efficacy in the treatment of pain than placebo. In some pre-determined
endpoints involving head-to-head comparisons, '381 was more effective than
celecoxib, the current market leader. An initial study in neuropathic pain also
suggested efficacy in this difficult-to-treat condition.
In these Phase II studies, the adverse event profile was similar to celecoxib,
and the overall safety evaluation supports progression to larger studies of
longer duration. The company will meet with regulatory agencies over the next
few months to finalise Phase III development plans, and will then have better
information on which to project a filing date for the product. GSK believes '381
has the potential to become a class-leading medicine for the treatment of pain.
DEPRESSION AND ANXIETY
Several new medicines to treat depression and anxiety in development.
Radafaxine (353162), a potent metabolite of bupropion, continues in development
as a treatment for depression. While results from Phase II clinical trials that
evaluated lower doses of radafaxine did not meet primary end points for
efficacy, the results of secondary endpoint analysis provide a basis for
undertaking further clinical studies at higher doses. The target date for
regulatory filing is 2007.
Importantly, in the completed Phase II trials for depression, weight loss was
observed in obese individuals after 8 weeks compared to a small weight gain
among patients on placebo. On the basis of these data, GSK is now planning to
develop this compound for the treatment of obesity.
GSK is also continuing to investigate two novel approaches for the treatment of
anxiety and depression. One explores the potential synergistic advantages of
combining low doses of 597599, an NK1 antagonist, and a low-dose SSRI in the
treatment of anxiety. A second approach focuses on 372475, a first-in-class,
potent, and selective serotonin, noradrenaline and dopamine reuptake inhibitor
being developed in partnership with NeuroSearch. With this compound, GSK expects
significant efficacy in depression with the potential to also improve cognitive
function.
MULTIPLE SCLEROSIS
The first oral integrin antagonist in development for MS.
683699, being developed in collaboration with Tanabe, is expected to be the
first oral integrin antagonist for the treatment of multiple sclerosis. In a
recent study, oral '699 matched the biomarker activity of intravenous Antegren -
the latest advance in the treatment of the disease. The compound is in Phase
IIb with filing expected in 2008.
ALZHEIMER'S DISEASE
Two novel therapies in development for neurodegenerative diseases.
GSK's 5-HT6 receptor antagonist, 742457, is highly brain penetrant, and has been
shown to enhance neurotransmitters and improve learning and memory in
pre-clinical models. The compound has recently completed Phase I testing, with
Phase II expected to begin in 2005.
GSK is also investigating Avandia for the treatment of Alzheimer's disease in
two clinical studies. Evidence suggests that PPARs (peroxisome proliferator
activated receptors) play a role in modulating CNS inflammation and glucose
metabolism, which may be important in Alzheimer's disease. Data already
published supports the concept that Avandia has an effect against Alzheimer's.
Therefore, GSK is conducting Phase IIb clinical trials with Avandia for the
treatment of Alzheimer's disease, with data from the first study expected in
2005.
SCHIZOPHRENIA
Talnetant: potential novel treatment with favourable tolerability.
Talnetant is an NK3 antagonist for the treatment of schizophrenia. In Phase II
studies, a small subset of patients with high exposures to the compound
experienced good efficacy with a benign safety and tolerability profile,
including lack of weight gain. A Phase II study is underway with a new
formulation that permits higher dosing; data is expected in 2005. Recent data
from this subset of patients also suggest that this compound has the potential
to deliver a cognitive benefit, which is increasingly recognised as a major
disability in schizophrenic patients.
2005-2007 CNS PRODUCT FILINGS
In addition to its promising CNS research compounds, GSK also showcased further
opportunities for near-term momentum with late-stage assets and currently
marketed products:
Lamictal: Having seen encouraging results in preliminary efficacy studies, GSK
is initiating a Phase III development programmeme for Lamictal for adjunctive
treatment of schizophrenia. In addition, Lamictal for the acute treatment of
bipolar disorder is expected to be filed in 2006. Lamictal XR, an improved
once-daily formulation, will also be filed for treatment of epilepsy in 2006,
and in 2007 for adjunctive treatment of schizophrenia and diabetic neuropathy.
Entereg: Currently physicians lack treatments for post operative ileus (POI), a
bowel impairment occurring after abdominal and other surgery that can be a major
contributing factor to patient discomfort (including nausea, vomiting, bloating
and constipation). POI can often prolong hospital stays, and may pose additional
costs to payers. Entereg (alvimopan) has been shown to accelerate
gastrointestinal (GI) recovery following abdominal surgery, allowing patients to
be ready to leave hospital sooner. The FDA has accepted for review an NDA for
Entereg in the management of POI. The FDA action date is April 25, 2005.
Entereg also appears to reduce the lower GI side effects of opioids without
interfering with the analgesic effects on the central nervous system. In
clinical trials, Adolor and GSK are studying Entereg for opioid-induced bowel
dysfunction - the constipation and the associated symptoms of chronic opioid use
- as well as chronic constipation. Phase IIb studies are ongoing, and NDA
submissions are targeted for 2007.
Trexima for Migraine: Developed in collaboration with Pozen, Trexima, an
innovative formulation combining the active ingredient in Imitrex - the current
market leader - and naproxen sodium, is expected to provide superior efficacy
compared to each of the individual components alone. In a Phase II trial, the
combination of Imitrex and naproxen sodium relieved pain more effectively than
either agent administered alone, both at the 2-hour time point, and on a
sustained basis from 2-24 hours. Filing is expected in 2H2005.
Requip/Adartrel in Restless Leg Syndrome (RLS): RLS is the third most common
cause of sleep disturbance. Treatment often focuses on symptom control, rather
than on the underlying condition; 50% of patients on medication are not treated
effectively. Phase III clinical data show that Requip/Adartrel reduced leg
movements and improved outcome measures like sleep and quality of life, in some
cases within one week of treatment. Requip/Adartrel was approved in France in
July 2004; GSK expects to gain US approval for the treatment of RLS in 1H2005.
GlaxoSmithKline, one of the world's leading research-based pharmaceutical and
healthcare companies, is committed to improving the quality of human life by
enabling people to do more, feel better and live longer. For more information,
please visit the company's web site at gsk.com.
Enquiries:
UK Media enquiries: Philip Thomson (020) 8047 5502
David Mawdsley (020) 8047 5502
Chris Hunter-Ward (020) 8047 5502
US Media enquiries: Nancy Pekarek (215) 751 7709
Mary Anne Rhyne (919) 483 2839
Patricia Seif (215) 751 7709
European Analyst/Investor enquiries: Duncan Learmouth (020) 8047 5540
Anita Kidgell (020) 8047 5542
US Analyst/ Investor enquiries: Frank Murdolo (215) 751 7002
Tom Curry (215) 751 5419
Under the safe harbour provisions of the US Private Securities Litigation Reform
Act of 1995, the company cautions investors that any forward-looking statements
or projections made by the company, including those made in this Announcement
and the Meeting presentation materials to which it relates, are subject to risks
and uncertainties that may cause actual results to differ materially from those
projected. Factors that may affect the Group's operations are described under
'Risk Factors' in the Operating and Financial Review and Prospects in the
GlaxoSmithKline Annual Report on Form 20-F for 2003.
Without limiting the foregoing, this Announcement and the Meeting presentation
materials to which it relates contain forward-looking statements regarding
ongoing drug discovery and development activities, the progress of which depends
in significant part on factors not fully within the Group's control, including
but not limited to the pace of clinical trial enrolment, the nature of the
results of pending and prospective preclinical and clinical trials, the
resolution of any unusual difficulties with drug formulation or manufacturing,
the outcome of review by regulatory authorities, changes in the prevailing legal
/regulatory climate, and the like. The Group's current expectations and other
information included in this Announcement and the related Meeting presentation
materials reflect data currently in hand, which may be preliminary in nature,
whereas the ultimate progress of investigational drugs through remaining stages
of development to regulatory submission, regulatory approval, and
commercialisation may differ materially, given inherent risks and uncertainties.
Brand names appearing in italics throughout this document are trade marks of GSK
or associated companies with the exception of Antegren, a trade mark of Elan
Pharmaceuticals; Entereg, a trade mark of Adolor Corporation; Vesicare, a trade
mark of Yamanouchi Pharmaceutical Co. Ltd.; and Boniva, a trade mark of F.
Hoffmann-LaRoche Ltd; which are used under licence by the Group.
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