SEPTEMBER 25th, 2003
Alzheimer's Drug from Merz Recommended for Approval in the USA
Frankfurt, September 25, 2003 - The Alzheimer's drug from Merz with the active ingredient Memantine
has been unanimously approved by all members of the Scientific Advisory Committee of US Federal Drug
Administration (FDA). Forest Laboratories, an American pharmaceutical company specializing in the
field of neurology and psychiatry, has acquired a license from Merz for the exclusive development
and marketing of this drug in the USA. The FDA will take the Scientific Committee's recommendation
into consideration in its decision regarding the approval of Memantine in the USA. The decision is
expected to be made by the end of 2003. A few months later, Memantine would be introduced to the
American market under the name Namenda.
"Memantine was approved in Europe last year in a central process under the trade name Axura®. It
already provides help for many patients in Europe with moderate to severe Alzheimer's disease who
previously had no possibilities for treatment," said Dr. Jochen Hückmann, Chief Executive Officer
of Merz Pharma GmbH & Co. KGaA. "We feel that today's vote of the Scientific Advisory Committee
fully confirms the positive results of our clinical studies and last year's decision of the European
approval authority. We now expect that Memantine will soon facilitate daily life for these patients,
their families, and their caregivers in the USA."
The Alzheimer's drug Axura® from Merz with the active ingredient Memantine is the first drug
worldwide that can be used to treat moderate to severe Alzheimer dementia. The drug significantly
facilitates the daily life of patients with advanced to severe Alzheimer's so that for example they
can eat by themselves again and wash themselves. Through the improved general conditions, the cost
of caregiving for each patient can be reduced by up to 10,000 euros a year, as Anders Wimo et al.
demonstrated this year in a study in Pharmaeconomics.*
"In several controlled clinical studies, Memantine proved its significant and lasting advantages for
patients with moderate to severe Alzheimer's disease," said Prof. Dr. med. Lawrence Olanoff,
Executive Vice President of Research and Development at Forest Laboratories. "Memantine is the first
active ingredient in a new generation of Alzheimer drugs with a mechanism of action that is very
different from previous therapeutic approaches. We will now work closely with the FDA in order to
achieve the approval of Memantine in the USA as quickly as possible. A few months later, Memantine
should then be available in the USA as well."
The Scientific Advisory Committee of the FDA, which encompassed experts from the fields of dementia
and other neurological disturbances, reviewed scientific data from two placebo-controlled Phase III
clinical studies conducted in the USA and one study conducted in Europe.
"A large number of people are already suffering from Alzheimer's today, but in the future the number
of patients will rise exponentially," said Dr. med. Steven DeKosky, Chairman of the Neurology
Department at the University of Pittsburgh and a presenter to the Scientific Advisory Committee.
"Right now, these people are left to face their disease alone. If Memantine is approved, this
innovative new therapy will finally be available for patients in the USA as well."
* Anders Wimo, Bengt Winblad, Albrecht Stöffler, Yvonne Wirth, Hans-Jörg Möbius,
Pharmacoeconomics 2003: 21 (5): 327-340
SEPTEMBER 1st, 2003
"I Can't Remember" Drugs to stave off age-induced memory impairment may be on the horizon
By Catherine Arnst Excerpt from Businessweek, September 1st, 2003
The 76-year-old California lawyer appears to be the very model of healthy aging. C.L., who asked
that his name not be used, hikes two miles up a nearby mountain four times a week, is always reading
two or more nonfiction books at a time, and boasts that his waist and chest measurements haven't
changed since he was 25. This take-charge guy expects a lot of himself. But for the past six years,
his memory hasn't measured up. He occasionally forgets a name, he loses his train of thought when
there are distractions, and he has walked away from six pairs of expensive sunglasses. "People who
are very well-trained intellectually notice when they begin to lose that ability to grab onto every
word, every concept," he says. "It's like a significant part of your life is erased."
Since more of us are living to an old, old age, trend lines for memory loss all point upward. The
Alzheimer's Assn. estimates that by 2050 -- when the number of people over 65 will have doubled, to
70 million -- there will be 13.2 million Alzheimer's victims. Run the numbers, and it's obvious that
a pill that promises to protect against this terrible malady would dwarf the $1.7 billion a
That such pills are even in the pipeline is something of a scientific miracle. The human brain is
medicine's most daunting frontier. Made up of more than one trillion highly complex neurons, it
remained obdurately opaque long after the body's other tissues had given up many of their mysteries.
But in the past decade, the code has been partially cracked. Using sophisticated imaging
technologies, animal experiments, and genetic insights, scientists now have a road map of the
complex process that is memory formation.
Products follow knowledge. The first drug able to improve the thinking abilities of people with
advanced Alzheimer's disease was approved in Europe last year and is widely expected to win the nod
from the Food & Drug Administration this fall. Memantine, developed by the German company Merz, is
no miracle cure, and it has shown no effect in Alzheimer's patients in the earliest stages of the
disease. But clinical trials demonstrated that the drug allows the most desperately confused
patients to live independently for six months to a year longer than they would otherwise, with no
debilitating side effects.
That's more significant than it may sound: Alzheimer's is the No.1 cause of institutionalization in
the U.S. Memantine marks the first big payoff of brain research carried out over the past decade.
The three treatments for Alzheimer's now on the market -- Pfizer's (PFE ) Aricept, Novartis' (NVS )
Exelon, and Reminyl from Johnson & Johnson (JNJ ) -- all boost the levels of a brain chemical called
acetylcholine, and first appeared in the early 1990s. These drugs can delay the downward trajectory
of patients in early stages of the disease for several months, but they do not improve thinking
power and can cause nausea, loss of appetite, and frequent bowel movements.
Memantine is a smart bomb by comparison. It targets a cell receptor that controls the intake of
glutamate, a neurochemical that scientists believe is responsible for 75% of the communications
between brain cells. "Memantine represents real progress, a meaningful therapeutic advance," says
Dr. Pierre Tariot, a University of Rochester psychiatrist.
Read the whole article
April 3rd , 2003
Study proves efficacy of Memantine drug from Merz in moderate to severe Alzheimer's disease
Frankfurt, April 3, 2003 – A study published today in the New England Journal of Medicine once
again reports on the efficacy of NMDA-antagonist Memantine in patients suffering from moderate to
severe Alzheimer dementia. Memantine proved to be significantly superior to placebo on three
independent levels: clinical global impression, cognitive performance, and activities of daily
living. At the same time, Memantine reduces caregiver time by more than 45 hours a month. This study
underscores the importance of Memantine as the first and only drug worldwide approved for the
treatment of the advanced stages of Alzheimer's disease.
The double-blind study randomized 252 patients from 32 centers in the United States to receive
either 20 mg of Memantine per day or matching placebo for 28 weeks. The Memantine-treated patients
showed significantly less decline in cognitive performance, measured by the Severe Impairment
Battery (SIB), than the placebo group. Activities of daily living, measured by ADCS-ADLsev*, were
also substantially less impaired in the Memantine group than in the placebo group. In addition,
researchers observed less deterioration of clinical global impression, measured by the CIBICplus**,
again significantly favoring Memantine.
Patients receiving Memantine also required considerably less caregiver time –
45.8 hours per month – than subjects receiving placebo, as assessed by the Resource Utilization in
Dementia (RUD) scale.
“Publication of these results by The New England Journal of Medicine demonstrates the importance
of this new and novel treatment for advanced Alzheimer’s disease,†said Dr. Jochen Hückmann,
Chief Executive Officer of Merz. “These data show how Memantine can offer therapeutic help for
millions of people facing Alzheimer’s disease worldwide who could not be helped before.â€
The superior treatment results were achieved regardless of severity staging. Both subgroups of
Alzheimer patients with moderate dementia and severe dementia showed an advantage regarding all
outcome measures.
Often reported adverse events were barely more frequent in the Memantine group than in the placebo
group. Medication was discontinued, due to adverse effects, almost twice as often (22 patients
vs.13) in the placebo group as in the Memantine group. In general, the authors concluded that “the
tolerability of Memantine in this study was found to be excellent.â€
About Memantine
Memantine is the first representative of a new class of Alzheimer drugs, an NMDA-receptor
antagonist. Memantine was developed by Merz and was recently approved in Europe by the EMEA for the
treatment of moderate to severe Alzheimer dementia. It is already available from Merz in Germany,
Austria, and Spain under the trademark Axura® and will be available in several other European
countries shortly as well as in other selected territories of the world.
Merz has licensed exclusive rights for Memantine to Forest Laboratories Inc. for the United States.
For a number of markets in Europe, Asia, Latin America as well as for Canada, Australia, and South
Africa, the exclusive rights have been granted to H. Lundbeck A/S. In several other countries, Merz
retains semi-exclusive marketing rights. To cover the Japanese market, Merz has agreed to an
exclusive partnership with Suntory-Daiichi for the development of Memantine in Japan.
About Merz
Merz Pharmaceuticals is an innovative pharmaceutical company specializing in the research and
marketing of drugs for the treatment of psychiatric and dermatological diseases. Merz is a leader in
the field of Alzheimer research and developed the first drug for the treatment of moderate to severe
Alzheimer's.
The Merz Group also includes Merz Consumer Care GmbH, a company that develops and markets innovative
health, beauty, and wellness products under the brand names Merz Spezial and tetesept, and Merz &
Krell, Europe's largest supplier of writing implements for the promotional products market.
The Merz Group has more than 1,700 employees and in fiscal 2001/02 generated about 320 million
euros in sales.
* ADCS-ADLsev = Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory
modified for severe dementia ** CIBICplus = Clinicians' Interview-Based Impression of Change plus
caregiver input.
March 25th , 2003
Tolerability of memantine in combination with cholinesterase inhibitors in dementia therapy
Hartmann S., Möbius HJ. International Clincial Psychopharmacology 18: 81 - 85 © (2003) Lippincott
Williams & Wilkins. (Abstract)
Februar 25th , 2003
Innovation for Alzheimer patients
Memantine about to be introduced throughout Europe
The NMDA receptor antagonist Memantine (Axura®) is going to be introduced in many countries in the
world for the first time for the treatment of advanced Alzheimer’s dementia. With the intro-
duction of this substance it is the very first time that a proven and effective treatment is
available for the treatment of the advanced stages of the commonest form of dementia. Experts from
the USA, UK, Germany and Spain have been discussing the substance’s properties at an international
symposium in Berlin with 300 phy-sicians from 15 countries.
“Memantine is an effective, safe and well tolerated treatment option for dementiaâ€, concluded
Prof. Steven Ferris of the Alzheimer’s Dis-ease Center at New York University. He presented two
studies which both demonstrated the significant efficacy of Memantine. The first study was a 6-month
double blind randomized two-arm multicenter study with the option of a 6-month open label extension.
A total of 252 patients with the diagnosis of “advanced Alzheimer’s dementia†took part in
this study. They received either 10 mg Memantine twice daily or placebo. After a study duration of
28 weeks the Memantine group demonstrated a significant improvement with respect to ADCS-ADLsev1 and
CIBIC-Plus2 compared to placebo. As the rate of adverse events was approximately the same in both
groups, it can be concluded that the side effect profile of Memantine is similar to that of placebo.
Combined treatment In practice, many patients in the advanced stages of dementia are al-ready being
treated with acetylcholinesterase inhibitors. In such cases it is worth adding Memantine, when the
disease is progressing. This was the conclusion of a combination study which was presented in Berlin
for the first time in Europe. 400 patients with moderately severe to severe Alzheimer’s dementia
on a stable dose of the acetylcho-linesterase inhibitor donepezil took part in this 6-month double
blind randomized placebo-controlled multicenter study. They received either 20 mg Memantine per day
or placebo additionally. The addition of Memantine was proven to be significantly superior to
donepezil alone in both of the defined endpoints. The cognitive capacity as measured by the SIB3
improved so much in the Memantine plus donepezil group that even after 24 weeks this was still
higher than the baseline value measured at the beginning of the study. The rate of adverse events
was not significantly different in the two groups. It can therefore be assumed that the two
medications can be administered in combination without any problems.
Efficacy in vascular dementia Memantine also leads to significant improvement in vascular demen-tia.
This is the result of two studies, which were presented by Profes-sor Rafael Blesa from the
University of Barcelona. In the first study, which was conducted in Great Britain, 579 patients with
the diagnosis of probable mild to moderate vascular dementia were randomized in a double blind study
to receive either 20 mg of Memantine per day or placebo for 28 weeks. In the second study, which was
conducted in France, 321 patients with the diagnosis of mild to moderate vascular dementia were
randomized in a 28-week double blind study and treated with either 10 mg of Memantine twice daily or
with placebo. Analysis of both studies showed a significant improvement in the ADAS-cog total
score4. The fact that Memantine is effective in the treatment of both vascular and Alzheimer’s
dementia is of great advantage in clinical practice. Obviously mixed forms of dementia occur very
often and make a differential diagnosis distinguishing between the two forms difficult.
Background Memantine belongs to a new class of medications for Alzheimer’s disease. It acts on the
glutamatergic transmitter system, which is one of the most important neurotransmitter systems in the
brain. As Prof. Johannes Kornhuber explained, Memantine modulates the N-methyl-D-aspartate NMDA)
receptor by blocking the effects of pathologi-cally elevated levels of glutamate but allows
physiological activation of the glutamate receptor. Thus, Memantine works in two ways against
Alzheimer’s dementia: on the one hand it improves symptoms, and on the other hand it is
potentially neuroprotective.
The substance Memantine was developed by the German company Merz Pharmaceuticals, located in
Frankfurt am Main. Merz has recently received approval for Axura® from the European Commission.
Axura® will be available in several European countries and other selected territories of the world.
Merz has licensed exclusive rights for Memantine to Forest Laboratories Inc. for the United States.
For a number of European markets as well as Canada, Australia and South Africa the exclusive rights
has been granted to H. Lundbeck A/S. For the remaining countries Lund-beck will co-market Memantine
with Merz. For Japan, Merz’ exclusive partner Suntory Ltd. is developing Memantine together with
Dai-ichi Pharmaceuticals.
References
Alzheimer’s Disease Cooperative Study Activities of Daily Living Inventory modified for severe
dementia Clinician’s Interview-Based Impression of Change plus caregiver input Severe Impairment
Battery Cognitive subscale of the Alzheimer’s Disease Assessment Scale
December 14th , 2002
New Memantine data show cognitive improvement in Alzheimer's patients treated with an
acetylcholinesterase inhibitor.
Berlin, 14th December 2002 (Merz Pharmaceuticals GmbH) - New, initial results from the first ever
controlled study to combine memantine (the first NMDA receptor antagonist licensed for the treatment
of Alzheimer's disease) with an acetylcholinesterase inhibitor were presented earlier this week at a
major meeting of neurology, psychiatry and pharmacology experts1. Patients treated with memantine
and donepezil showed improvement in cognitive function where as donepezil and placebo treated
patients were associated with cognitive decline over the six-month trial.
Researchers reported that the group of patients treated with memantine and donepezil for six months
showed significant improvement in cognitive function compared to donepezil and placebo treated
patients as measured by the Severe Impairment Battery (SIB). By comparison, cognitive function for
patients on donepezil and placebo treatment continued to decline relative to their baseline status.
The difference between the two treatment groups was statistically significant as endpoint.
This six-month, phase III, multi-center, randomised, placebo-controlled trial of more than 400
patients with moderate to severe Alzheimer's disease in the US also showed statistically significant
benefits in function (activities of daily living) according to the Alzheimer's Disease Cooperative
Study Inventory-Activities of Daily Living (ADCS-ADL) assessment scale (p = 0.028) and global
response (overall improvement) as measured on the Clinician's Interview-Based Impressions of Change-
Plus (CIBIC-Plus) (p = 0.027) in the memantine and donepezil group as compared to patients treated
with donepezil and placebo. "This study clearly demonstrates that the combination of memantine
offers a new form of treatment for patients with Alzheimer's disease," said Pierre Tariot,
M.D, the study's lead author and Professor of Psychiatry, Medicine and Neurology at the University
of Rochester. "The results and implications are important for several reasons. First, the field is
truly desperate for treatment advances for this debilitating illness. Second, memantine has a
mechanism of action that is distinct from cholinesterase inhibitors, meaning that different
aspects of the pathophysiology of the illness are being treated. Third, memantine provides
cognitive and functional benefit in patients already taking donepezil. This superior outcome is
both encouraging and exciting. "If memantine is approved -Sic. (in the US), I believe that its use
may become the standard of care in patients with moderate to severe Alzheimer's disease," said
Ma. Tariot.
Memantine, is the only EU approved agent indicated for the treatment of moderately severe to severe
Alzheimer's disease. Previous trials comparing Memantine with placebo, have demonstrated clinically
significant improvements in cognition (memory and thought processes), function (activities of daily
living), and global response (overall improvement)2,3. Benefits with Memantine treatment have also
been shown to continue for at least 12 months4.
These results translated into clear benefits for patients and their carers, allowing greater
independence for patients, therefore delaying admission to long-term care2,3. There was also a
reduction in time spent by carers of more than one working week per month (52 hours)5. In two key
trials, patients on Memantine were more able to recognise relatives and hold short conversations,
making everyday life easier2,3. Patients taking Memantine experienced no more side effects than
those taking placebo.
Memantine represents a new opportunity to even treat the more severe stages of Alzheimer's disease6.
This is extremely significant because there are no other agents available for the more severe stages
of Alzheimer's disease and 75% of the treatment costs of demented patients relate to this stages7.
Memantine is marketed under the trade name AXURA®is marketed by Merz Pharmaceuticals GmbH, a
specialty pharmaceuticals company engaged in the research and development, production, marketing and
sale of drugs for the treatment of neurology and psychiatric as well as metabolic disorders and
dermatology.
Forest Laboratories plans to submit an amended New Drug Application (NDA) to the U.S. Food and
Drug Administration (FDA) for memantine as a treatment for moderate to severe Alzheimer's before
the end of 2002.
References
Forest Laboratories, Inc. PR Newswire Dec 9, 2002. Reisberg B, Stöffler A, Ferris S, Schmitt F,
Doody RS, Möbius H-J. A placebo controlled study of memantine in advanced Alzheimer's disease.
Abstract presented at the fifteenth Annual Meeting of the American Association of Geriatric
Psychiatry, February 24-27, 2002, Orlando, Florida Winblad B, Poritis N. Memantine in severe
dementia: results of the 9M-Best study (Benefit and Efficacy in Severely Demented Patients During
Treatment with Memantine). Int J Geriatric Psychiatry 1999; 14: 135-146 Reisberg B, Möbius H-J,
Stöffler A, Schmitt F, Doody R, Ferris SH. Long-term treatment with the NMDA antagonist, memantine:
results of a 24-week, open-label extension study in advanced Alzheimer's disease. Abstract presented
at the International Conference on Alzheimer's Disease and Related Disorders, July 20-25, 2002,
Stockholm, Sweden Wimo A, Winblad B et al. Effect of long-term treatment with Memantine, an NMDA
antagonist, on costs associated with advanced Alzheimer's disease: Results of a 28-week, randomized,
double-blind, placebo-controlled study. Presented at the 8th International Conference on Alzheimer's
Disease and related disorders, July 20-25 2002, Stockholm, Sweden Memantine Tablets.Summary of
Product Characteristics, May 2002. Memantine Solution. Summary of Product Characteristics, May 2002
Wimo A, Winblad B. Health economic aspects of Alzheimer's disease and it's treatment.
Psychogeriatrics 2001; 3:189-9
November 15th , 2002
A double blind placebo-controlled multicentre study of memantine in mild to moderate vascular
dementia (MMM 500)
Clin Psychopharmacol (2002) 17, 297-305 Wilcock 2002 (MMM 500)
September 22nd , 2002
Efficacy and safety of memantine in patients with mild to moderate vascular dementia (MMM 300)
New data of a double blind study. Stroke (2002) 33:1834-1839
Orgogozo & Forette 2002 (MMM 300)
August 1st, 2002
Merz Pharmaceuticals launches AXURA® for the treatment of Alzheimer`s disease
Alzheimer's disease is the most common form of dementia. Late-stage patients represent a substantial
proportion of the total Alzheimer's population. Despite a stable prevalence rate, the 8.3 million
Alzheimer's disease patients in 1998 in the U.S., Japan and Europe (Germany, UK, France, Italy,
Spain) is expected to increase to 10.2 million by 2008, due to the growing number of senior citizens
in these countries. According to the Alzheimer's Association, it is projected that by 2050 more than
14 million people may develop Alzheimer's disease in the U.S. alone. Merz has received approval for
AXURA® for the treatment of moderately severe and severe Alzheimer´s disease from the European
Commission. The NMDA receptor antagonists memantine demonstrates clinically significant efficacy in
patients with moderately severe and severe Alzheimer's disease. Starting with Germany in August
2002, AXURA ® will become available in several European countries and other selected territories of
the world.
July 25th, 2002
AXURA® demonstrates benefits for the treatment of Alzheimer's Disease
At the Alzheimer's Association 8th International Conference on Alzheimer's Disease and Related
Disorders held in Stockholm July 20-25 new data associated with Merz Pharmaceuticals AXURA® were
presented. In preclinical as well as clinical studies, treatment with AXURA® (active ingredient
Memantine) demonstrated a number of potential benefits in the treatment of Alzheimer's disease:
sustained clinical efficacy over the period of 1 year, reduced caregiver burden and reduced societal
costs, good tolerability in combination with cholinesterase inhibitors and neuroprotective effects
in pre-clinical models and factors of neurodegeneration.
In an oral presentation, Barry Reisberg M.D., Professor of the Department of Psychiatry, New York
University School of Medicine, presented data supporting sustained efficacy of AXURA® over the
period of 52 weeks in treatment of Alzheimer's disease. In the 24 weeks open label extension phase,
the former placebo patients who switched to Memantine showed improvement in cognitive, functional
and global domains compared to the projected rate of decline. This open extension study was preceded
by a 28 weeks, multi-center, double blind, placebo-controlled trial with 252 patients. AXURA® was
well tolerated throughout the study with an overall incidence of adverse events nearly similar to
patients treated with placebo.
An additional pharmacoeconomical analysis of the above mentioned study conducted by Prof. Anders
Wimo M.D., Associate Professor of Family Medicine, Stockholm University, revealed that treatment
with AXURA® reduces the time commitment and costs associated with caring for an Alzheimer's disease
patient. Furthermore it was demonstrated that the treatment with AXURA® is associated with a
significant reduction in caregiver time of about 50 hours per month compared to placebo. In
addition, the number of patients institutionalized due to the progression of their disease was lower
in the AXURA® treatment group compared to placebo.
"The Alzheimer's patient caregiver faces physical, emotional and financial challenges on a daily
basis," said Prof. Wimo. "Our research found that AXURA® therapy in Alzheimer's patients in the
moderate to severe stages eased some of the time commitment and financial constraints placed on
caregivers, providing financial benefit and more spare time."
Alzheimer's disease is the most common form of dementia. Late-stage patients represent a substantial
proportion of the total Alzheimer's population and cause the main portion of costs to society.
Despite a stable prevalence rate, the 8.3 million Alzheimer's disease patients in 1998 in the U.S.,
Japan and Europe (Germany, UK, France, Italy, Spain) is expected to increase to 10.2 million by
2008, due to the growing number of senior citizens in these countries. According to the Alzheimer's
Association, it is projected that by 2050 more than 14 million people may develop Alzheimer's
disease in the U.S. alone.
In another study performed by Merz, the tolerability of a combination of AXURA® with cholinesterase
inhibitors in patients with Alzheimer's disease and vascular dementia was addressed. The study
showed that this combination treatment was well tolerated.
Evidence for AXURA's® neuroprotective potential was further supported by the results of three pre-
clinical studies, also presented at the meeting. Scientists selected various experimental models to
test the ability of AXURA® to protect neurons in rats. The results suggested that AXURA® may
prevent cell death associated with glutamate neurotoxicity. The neurotransmitter glutamate plays an
integral role in neural pathways associated with learning and memory. The excitotoxicity produced by
excessive amounts of glutamate is hypothesized to be responsible for the neuronal cell death
observed in Alzheimer's. Results presented at the meeting suggest that AXURA® may exert a
neuroprotective effect on neurons, and slows neuronal decay when beta-amyloid is present. It is
thought that the formation of beta-amyloid containing plaques in the brain and thus progressive nerve-
cell death are a primary cause of the cognitive and functional deterioration in Alzheimer's disease.
Furthermore, it was reported that AXURA® restores tau hyperphosphorylation in an experimental
model. Abnormal hyperphosphorylation of tau and consequently neurofibrillary degeneration is another
pathway believed to be involved in Alzheimer's disease progression.
AXURA® is the first in a new class of drugs for Alzheimer's disease, NMDA receptor antagonists,
demonstrating clinically significant efficacy in patients with moderately severe and severe
Alzheimer's disease. AXURA® is expected to fulfil unmet needs within this group of patients - for
whom no approved treatment has been available until now. Merz has recently received approval for
AXURA® from the European Commission. AXURA® will be available in several European countries and
other selected territories of the world, starting with Germany in August 2002.