SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 6-K
REPORT OF FOREIGN PRIVATE ISSUER
PURSUANT TO RULE 13a-16 or 15d-16 OF
THE SECURITIES EXCHANGE ACT OF 1934
Report on Form 6-K for the month of April 2002
Novartis AG
(Name of Registrant)
Lichtstrasse 35
4056 Basel
Switzerland
(Address of Principal Executive Offices)
Indicate by check mark whether the registrant files or will file annual reports
under cover of Form 20-F or Form 40-F.
Form 20-F X Form 40-F
--- ---
Indicate by check mark whether the registrant by furnishing the information
contained in this form is also thereby furnishing the information to the
Commission pursuant to Rule 12g3-2(b) under the Securities Exchange Act of 1934.
Yes No X
--- ---
Enclosures:
1. Novartis publishes evidence that dipeptidyl peptidase IV (DPP IV)
inhibition lowers blood glucose in type 2 diabetes patients (April 29,
2002)
2. Novartis receives positive opinion from CPMP for Zometa(R)for the treatment
of cancer-related bone complications (April 26, 2002)
3. Novartis' life-saving malaria treatment Coartem(R)added to the WHO
Essential Medicines List (April 24, 2002)
4. Alzheimer's patients who fail on Aricept(R)(Donepezil) may benefit from
Exelon(R)(Rivastigmine) (April 24, 2002)
5. Early detection is key to maximizing vision outcomes in age related macular
degeneration (April 23, 2002)
Page 1 of 35 Pages
6. Novartis and QLT file new drug application in Japan, for Visudyne(R)(April
23, 2002)
7. Exciting data suggest that adding entacapone from the first dose of
levodopa therapy may delay the emergence of dyskinesia in Parkinson's
disease (April 19, 2002)
8. Novartis addresses ethical challenges of stem cell research (April 18,
2002)
9. Novartis drug Glivec(R)now also approved in Switzerland for treatment of
life-threatening kind of gastrointestinal cancer (April 15, 2002)
10. New immunosuppressant CerticanTM addresses a key risk factor in late graft
loss - First ever clinical data for an immunosuppressant to show a
significant reduction in vasculopathy (April 12, 2002)
11. Novartis researchers honored by American Association for Cancer Research
for discovery work on Glivec(R) (April 9, 2002)
12. Novartis launches world's smallest ERT patch in Germany - its first major
European market (April 9, 2002)
13. Studies show long-term benefits of Exelon(R)(rivastigmine) in Alzheimer's
disease (April 5, 2002)
14. Study shows Elidel(R)Cream 1% significantly improves eczema signs and
symptoms in patients with mild to moderate disease (April 2, 2002)
Page 2 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
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Novartis publishes evidence that dipeptidyl peptidase IV (DPP IV) inhibition
lowers blood glucose in type 2 diabetes patients
Proof-of-concept published in 'Diabetes Care' could pave the way to development
of new class of diabetes treatment
Basel, Switzerland, 29 April - Evidence that a new pharmacological strategy may
be a useful treatment for type 2 diabetes is being published in the May issue of
Diabetes Care. Initial findings from a study in patients with type 2 diabetes
show that inhibition of the enzyme dipeptidyl peptidase IV (DPP IV) improves
glucose tolerance and insulin response to oral glucose in patients with type 2
diabetes.
"These encouraging results strongly support further pharmacological development
of DPP IV inhibition in the treatment of type 2 diabetes. We are looking at
potential development candidates in this field, the most advanced being LAF
237A, which is currently in Phase II of clinical development" said James
Shannon, worldwide Head of Clinical Development at Novartis Pharma AG, who
sponsored the study. "Novartis is committed to exploring innovative treatments
for this disease, which continues to affect a ever-increasing number of people
around the world."
The study sought to determine whether DPP IV inhibition could improve blood
sugar control in patients with type 2 diabetes by inhibiting the breakdown of
the naturally-occurring hormone GLP-1 (glucagon-like peptide-1). GLP-1 is
released into the gut after food is eaten and results in increased insulin
secretion, delayed glucose absorption and reduced glucose output from the liver,
all of which help to control blood glucose. However, GLP-1 circulates in the
body for just a few minutes before it is broken down by the naturally-occurring
DPP IV enzyme. The inhibition of DPP IV thus raises levels and prolongs the
availability of GLP-1.
In the double-blind, multicenter study, men and women (n=141) with a history of
type 2 diabetes (HbA1c 7.4%) were randomized evenly to receive either placebo or
an orally active and highly selective DPP IV inhibitor, at 100 mg three times
daily or 150 mg twice daily.
After a 4-week treatment period, mean 24-hour glucose levels, fasting glucose
levels, and prandial glucose excursions (increases in glucose levels after
eating) were reduced in the group of patients who received the experimental
drug.
The reduction in the 24-hour mean glucose was -1.0 mmol/l (95% Cl -1.4, -0.7
mmol/l; p<0.001) for patients receiving 100 mg, and was -1.0 mmol/l (-1.4, -0.6
mmol/l; p<0.001) for patients
Page 3 of 35 Pages
receiving 150 mg. Fasting glucose levels were significantly reduced, as 35% of
the patients given 100 mg, and 37% of those given 150 mg, achieved a fasting
plasma glucose level of <7 mmol/l, versus only 3% in the placebo group. Compared
with placebo, prandial glucose excursions were reduced by -1.2 mmol/l in the 100
mg group (-1.7, -0.7 mmol/l; p<0.001) and by -1.3 mmol/l in the 150 mg group
(-1.8, -0.7 mmol/l; p<0.001).
Overall, the test compound was well tolerated in this study. There was one case
of confirmed hypoglycemia (low blood sugar).
The DPP IV inhibitor used in the study was Novartis' NVP DPP728. Further
long-term studies are necessary to fully evaluate DPP IV inhibitors. Novartis is
developing LAF 237A - a related DPP IV inhibitor that is currently in Phase II
of clinical development and may offer formulation and dosing advantages.
"An oral agent that harnesses the therapeutic potential of GLP-1 could represent
an important advance in treatment of diabetes type 2 at a relatively early stage
in the disease," said Bo Ahren, MD, Head, Research Department, Lund University
Hospital, Sweden, and lead author of the study. "Early treatment with agents,
like DPP IV inhibitors could circumvent the potential long-term consequences
that can be debilitating and, sometimes, fatal - such as diabetic retinopathy,
diabetic foot disease, kidney failure and heart disease."
According to the World Health Organization, more than 150 million people have
diabetes worldwide, and type 2, or non-insulin-dependent diabetes mellitus, is
the most common form and accounts for around 90% of all cases.
The foregoing press release contains forward-looking statements which can be
identified by terminology such as "evidence," "could," "improves," "encouraging
results," "exploring innovative treatments," "extending its effectiveness",
"strongly support further pharmacological development", "committed", "effective
long-term management", "consistently improving", "suggest," "would," "advance"
"could," "potential" or similar expressions. Such forward looking statements
involve known and unknown risks, uncertainties and other factors that may cause
the actual results to be materially different from any future results,
performance, or achievements expressed or implied by such statements.
Commercialization of NVP DPP728 can be affected by, amongst other things,
uncertainties relating to results of additional clinical trials, product
development, regulatory actions or delays or government regulation generally,
the ability to obtain or maintain patent or other proprietary intellectual
property protection and competition in general, as well as factors discussed in
the Company's Form 20-F filed with the US Securities and Exchange Commission.
Should one or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary materially from
those described herein as anticipated, believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 4 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
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Novartis receives positive opinion from CPMP for Zometa(R) for the treatment of
cancer-related bone complications
Basel, 26 April 2002 - Novartis announced today that it has received a positive
opinion from the Committee for Proprietary Medicinal Products (CPMP) for
Zometa(R) (zoledronic acid) for the prevention of skeletal related events in
patients with advanced malignancies involving bone. These malignancies include
multiple myeloma, prostate cancer, breast cancer, lung cancer and other solid
tumour types. Zometa offers patients and clinicians a highly effective treatment
with a convenient 15-minute infusion time.
"When cancer spreads to other parts of the body, one of the most common sites
is the bone. The result can be complications such as fractures and spinal cord
compression, which can be extremely debilitating and life-threatening in the
latter case. In clinical studies, Zometa helps prevent these complications, thus
significantly improving the patients' quality of life", said Robert E. Coleman,
Section Head Clinical Oncology, University of Sheffield, United Kingdom.
The European Union (EU) Commission usually grants approval of products three to
four months after a CPMP positive opinion. Novartis submitted the initial
application for the use of Zometa in this indication to the European Agency for
the Evaluation of Medicinal Products (EMEA) on 30 July 2001. In February, the
U.S. Food and Drug Administration (FDA) granted approval for use of Zometa in
treating patients with multiple myeloma and patients with documented bone
metastases from solid tumours, in conjunction with standard antineoplastic
therapy.
"Novartis is pleased the CPMP has recommended approval of Zometa in the
treatment of bone metastases in a broad range of tumour types based on the
favourable results of the clinical trials," said David Epstein, President,
Novartis Oncology. " Zometa offers physicians and patients a more convenient
therapy to effectively manage a serious complication of their disease."
The application for Zometa is based on data from three large international
clinical trials evaluating more than 3,000 patients with myeloma, breast cancer,
prostate cancer, lung cancer and other solid tumours. This is the largest set of
clinical trials ever conducted to evaluate the efficacy and tolerability of a
bisphosphonate in treating cancerous bone lesions.
About Zometa
Zometa is a new generation intravenous (IV) bisphosphonate. Novartis has
previously received marketing clearance for Zometa in the treatment of
hypercalcaemia of malignancy (HCM), also
Page 5 of 35 Pages
known as tumour-induced hypercalcaemia (TIH), in the European Union and in more
than 65 countries.
Contraindications and Adverse Events
In clinical trials in patients with bone metastases, Zometa was generally well
tolerated, with a safety profile similar to other bisphosphonates. The most
commonly reported adverse events included flu-like syndrome (fever, arthralgias,
myalgias, skeletal pain), fatigue, gastrointestinal reactions, anaemia,
weakness, cough, dyspnoea and oedema. Zometa should not be used during pregnancy
and in breast-feeding women. Zometa is contraindicated in patients with
clinically significant hypersensitivity to zoledronic acid or other
bisphosphonates, or any of the excipients in the formulation of Zometa.
Zometa and other intravenous bisphosphonates have been associated with reports
of renal insufficiency. As with other (i.v.) bisphosphonates, renal monitoring
is recommended, for instance serum creatinine, prior to each dose. Caution is
advised when Zometa is administered with other potentially nephrotoxic drugs.
Doses of Zometa should not exceed 4 mg and the duration of infusion should be no
less than 15 minutes.
This release contains certain forward-looking statements relating to the
Company's business, which can be identified by the use of forward-looking
terminology such as "usually grants approval", or similar expressions, or by
discussions regarding potential new indications for existing products. Such
forward-looking statements involve known and unknown risks, uncertainties and
other factors that may cause actual results to be materially different from any
future results, performance or achievements expressed or implied by such
statements. There are no guarantees that any of the potential new indications
will be commercialized in any market. Any such commercialization can be affected
by, among other things, uncertainties relating to product development and
clinical trials, regulatory actions or delays or government regulation
generally, the ability to obtain or maintain patent or other proprietary
intellectual property protection and competition in general, as well as factors
discussed in Novartis AG's Form 20-F filed with the U.S. Securities and Exchange
Commission. Should one or more of these risks or uncertainties materialise, or
should underlying assumptions prove incorrect, actual results may vary
materially from those described herein as anticipated, believed, estimated or
expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 6 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
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Novartis' life-saving malaria treatment Coartem(R) added to the WHO Essential
Medicines List
Basel, 24 April 2002 - Coartem(R) (artemether/lumefantrine), the novel,
life-saving malaria treatment, is now included in the World Health
Organization's Model List of Essential Medicines.
The first fixed-dose, artemisinine combination antimalarial, Coartem is being
provided at cost by Novartis and distributed through the WHO as part of the
worldwide 'Roll Back Malaria' initiative.
It's only the third time that the WHO's Expert Committee on the Use of Essential
Medicines has added a branded, patent-protected pharmaceutical to its list which
many developing countries use as a model national formulary. Admission to the
list follows a vigorous, data-driven review and acknowledges Coartem's safety,
efficacy and cost-effectiveness.
"Over 1 million people die of malaria each year, many of them children. In
addition, endemic countries suffer a great burden with over 30% of hospital beds
in some areas occupied by Malaria patients and about 300-500 million new cases
each year. When we saw the outstanding efficacy of Coartem with cure rates above
95% even in areas of multi-drug resistance, we determined to make Coartem
available at cost for patients in developing countries," said Dr. Daniel
Vasella, Chairman and CEO of Novartis. "We are grateful to the WHO and in
particular to Dr. Gro Harlem Brundtland and Dr. David Heymann, for their
excellent cooperation as we all worked to ensure that patients in need had
access to a modern and effective therapy. We hope that our collaboration with
WHO can serve as a model for future public/private partnerships."
Many different antimalarial medications have been used successfully in the past
but malarial parasites in several regions have become resistant, particularly in
parts of Southeast Asia where multi-drug resistance is extremely high. Coartem
is the fastest-acting antimalarial therapy and by virtue of its excellent
tolerability, it can be administered to small children, the largest population
at risk.
Manufactured by Novartis in China, Coartem was co-developed by Novartis and
Chinese researchers at the Institute of Microbiology and Epidemiology in
Beijing. Coartem contains the same ingredients as Riamet, a Novartis medication
approved in Europe for travellers visiting malaria-endemic regions.
Page 7 of 35 Pages
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 8 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
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Alzheimer's patients who fail on Aricept(R)(Donepezil) may benefit from
Exelon(R)(Rivastigmine)
Basel, 24 April, 2002 - More than half (56 percent) of Alzheimer's disease
patients who had failed to show sustained benefit from treatment with Aricept(R)
(donepezil) therapy may benefit from treatment with Exelon(R) (rivastigmine,
Novartis), according to a new multicenter study(1) published in this month's
issue of Current Medical Research and Opinion. Both drugs are members of a class
called cholinesterase inhibitors, currently the only type of drug approved for
the treatment of mild to moderate Alzheimer's disease (AD).
The findings suggest a new approach to treating AD: switching to another
cholinesterase inhibitor if one agent fails. Switching therapies is common in
managing many diseases, but not currently in the treatment of AD because many
physicians assume - apparently incorrectly - that all cholinesterase inhibitor
drugs are similar. If a patient fails on one agent, it is often assumed another
agent would be equally ineffective, so cholinesterase inhibitor therapy is
discontinued all together.
"Our findings show switching patients from one cholinesterase inhibitor to
another - in this case, from donepezil to Exelon - can be a valuable therapeutic
strategy, offering renewed hope to physicians, AD patients and caregivers
alike," said Sophie Auriacombe, MD, the lead author of the study at the Clinique
St. Augustin in Bordeaux, France. She and her colleagues decided to study
switching patients to Exelon because "it has a number of characteristics that
make it an especially attractive treatment for AD," she said.
Although its exact causes are not understood, AD is associated with decreased
transmission of signals between nerves in the brain, especially those that rely
on the neurotransmitter acetylcholine. Exelon is unique because it treats AD by
inhibiting the two key enzymes that breakdown acetylcholine -
acetylcholinesterase and butyrylcholinesterase - thus prolonging the
neurotransmitter's action. Other drugs commonly used to treat AD, such as
donepezil and galantamine, inhibit acetylcholinesterase but not
butyrylcholinesterase. Recent research suggests that butyrylcholinesterase may
play an increasingly important role in regulating acetylcholine levels as AD
progresses, and that the dual inhibitory action of Exelon may provide greater
and more sustained efficacy in treating patients with the disorder.(2) In
addition, unlike donepezil,(3,4) long-term use of Exelon does not increase
target enzyme activity, which can lead to decreased inhibition and, possibly,
diminished effectiveness.
Study and Findings
Involving 91 specialist treatment centers in France, the prospective, open-label
study evaluated the efficacy and safety of six months of rivastigmine therapy in
382 outpatients with mild to
Page 9 of 35 Pages
moderately severe AD who, within the previous 12 months, had failed to show
sustained benefit from treatment with donepezil (80% due to lack of efficacy,
11% due to tolerability problems, and 9% for both reasons). Lack of sustained
benefit was shown over at least a six-month period by a decline in scores on a
short, standard test of cognitive function (the Mini-Mental State Examination)
or a noticeable loss of ability to function. Because AD usually progresses
slowly, changes in the status of patients often require at least six months to
be observable.
On average, the patients had Alzheimer's disease for two years, and had been
previously treated with donepezil for 14 months (10 mg/day for most patients, or
5 mg/day if the higher dose was poorly tolerated). Donepezil treatment was
discontinued for at least seven days and up to a maximum of three months before
the start of rivastigmine therapy.
Patients began treatment with rivastigmine 1.5 mg b.i.d. and, after four weeks
in most cases, the dosage was progressively increased by 3 mg/day every four
weeks, up to a maximum of 12 mg/day. By the end of the study, most patients
(91.4%) were receiving > or = to 6 mg/day, with more than one-third (38.4%)
receiving 12 mg/day.
At the study's completion, 56.2% of patients responded to rivastigmine by either
stabilizing (30.1%) or improving (26.1%) based on physicians' assessments (the
Clinicians' Global Impression of Change). Cognitive performance (measured by the
Mini-Mental State Examination) and the ability to perform activities of daily
living (measured by Instrumental Activities of Daily Living scale) improved or
stabilized in 48.9% and 57.0% of patients, respectively.
Rivastigmine was generally well tolerated; the most common adverse events were
nausea and vomiting, consistent with reports from previous clinical studies.
Serious adverse events related to rivastigmine were reported in 2.4% of
patients. Most (84.6%) who experienced tolerability problems with donepezil
tolerated rivastigmine treatment for the full study duration, and more than half
(54.5%) who discontinued donepezil treatment due to lack of efficacy responded
to rivastigmine.
"The benefits of Exelon seen in these patients who failed on donepezil may be
due to Exelon's unique, dual inhibitory action and other characteristics, and
the gradual dose escalation made the treatment highly tolerable," said Dr.
Auriacombe. She said that, taken together with other evidence,(5,6) the study's
findings "provide strong support for physicians to consider switching
cholinesterase therapies when patients fail on one agent - particularly
switching to Exelon if patients fail on donepezil," she said.
About Alzheimer's Disease
Alzheimer's disease (AD) is a progressive, degenerative disease that alters the
brain, causing impaired memory, thinking and behaviour. Affecting approximately
15 million people worldwide and 5 to 10 percent of those over 65 years of age,
it is the most common form of dementia and the leading cause of death after
cardiovascular disease and cancer.
This press release contains forward looking statements which can be identified
by the use of forward-looking terminology such as "suggest", new and better
approach", "valuable therapeutic strategy", "especially attractive treatment",
"may", "strong support" or similar expressions. Such forward looking statements
involve known and unknown risks, uncertainties and other factors that may cause
actual results to be materially different from any future results, performance
or achievements expressed or implied by such statements. Any commercialisation
can be affected by, amongst other things, uncertainties relating to product
development, regulatory actions or delays or government regulation generally,
the ability to obtain or maintain patent or other proprietary intellectual
property protection and competition in general, as well as factors discussed in
Novartis
Page 10 of 35 Pages
AG's Form 20F filed with the Securities and Exchange Commission. Any of these
and other factors can cause the actual results to differ materially from the
expected or predicted results.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
1 Auriacombe S, Vellas B, Pere J-J, Loria-Kanza Y. Efficacy and safety of
rivastigmine in patients with Alzheimer's disease who failed to benefit
from treatment with donepezil. CMRO 2002; 18; 129-138.
2 Ballard CG. Advances in the treatment of Alzheimer's disease: benefits
of dual cholinesterase inhibition. Eur Neurol 2002; 2002;47(1):64-70.
3 Davidsson P, Blennow K, Andreasen N, Eriksson B, Minthon L, Hesse C.
Differential increase in cerebrospinal fluid acetylcholinesterase after
treatment with acetylcholinesterase inhibitors in patients with
Alzheimer's disease. Neurosci Lett 2001;300:157-60.
4 Amici S, Lanari A, Romani R, Antognelli C, Gallai V, Parnetti L.
Cerebrospinal fluid acetylcholinesterase activity after long-term
treatment with donepezil and rivastigmine. Mech Ageing Dev
2001;122:2057-62.
5 Bullock R, Connolly C. Switching cholinesterase inhibitory therapy in
Alzheimer's disease - UK experience. Poster presented at Pathways from
science to effective patient management in dementia meeting. Istanbul,
Turkey: 23-25 March, 2001.
6 Shua-Haim JR, Smith JM, Amin S. Crossover results from donepezil to
rivastigmine in Alzheimer's disease patients: an overall analysis of
three prospective studies. J Am Geriatr Soc 2001;49:S115.
Page 11 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
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MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
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Early detection is key to maximizing vision outcomes in age related macular
degeneration
New analysis demonstrates lesions detected earlier may help patients benefit
more from Visudyne(R) therapy
Basel, 23 April 2002 -- Novartis Ophthalmics, the eye health unit of Novartis,
and QLT Inc. report that Neovascular age-related macular degeneration (AMD)
patients may have improved benefits with Visudyne(R) (verteporfin) therapy if
the condition is detected early when the lesion size is considered smaller.
Visudyne is the only drug approved for some forms of wet AMD. Although Visudyne
therapy is effective in various lesion sizes, the amount of vision preserved
compared with no treatment may be greater by two lines if presented early. The
results of these exploratory analyses were presented today at the International
Congress of Ophthalmology in Sydney, Australia.
"These analyses should encourage the ophthalmic community to consider seeking
and detecting the neovascular form of AMD early in its disease course," states
Neil M. Bressler, MD, of the James P. Gills Professor of Ophthalmology at The
Wilmer Ophthalmological Institute of The Johns Hopkins University School of
Medicine and chair of the clinical centers that undertook the randomized
clinical trials providing these new analyses. "This is increasingly important
with the growing number of people each year developing neovascular AMD", Dr.
Bressler further stated.
Exploratory analyses showed that in Visudyne-treated lesions with a
predominantly classic or minimally classic composition the mean visual acuity
loss in the smallest lesions was about half of that in the largest lesions, and
in occult with no classic lesions it was nearly four times less than the largest
lesions. These analyses were conducted in patients with predominantly classic
(n=242) or minimally classic lesions (n=306) at enrollment in the Treatment of
AMD with Photodynamic therapy (TAP) Investigation and AMD patients with occult
with no classic CNV (n=258) in the Verteporfin In Photodynamic therapy (VIP)
Trial. Baseline characteristics of patients among these three lesion types were
compared. Analysis of covariance (ANCOVA) was used to explore the effect of
baseline lesion size, visual acuity, and lesion composition on the change in
visual acuity from baseline. When different lesion compositions were included in
the ANCOVA model, lesion size was an important factor affecting treatment
benefit, and appeared potentially to be more important than either lesion
composition as identified on fluorescein angiography or visual acuity at
baseline.
Page 12 of 35 Pages
In the review, the mean size of predominantly classic lesions (3.4 MPS disc
areas [DA]) was smaller than for minimally classic (4.7 MPS DA) and occult with
no classic lesions (4.3 MPS DA). In addition, the proportion of smaller lesions
(< or = to MPS DA) was significantly greater in patients with predominantly
classic (65%) than in minimally classic (39%) or occult with no classic (47%)
lesions. In the ANCOVA of individual lesion types, there was a significant
treatment-by-lesion-size interaction for minimally classic and occult with no
classic lesions, but not for predominantly classic lesions, as those lesion
sizes at baseline were relatively small. Interactions between treatment and
baseline visual acuity were not significant. Smaller (< or = to MPS DA)
minimally classic and occult with no classic lesions seemed to have similar
visual acuity outcomes (mean loss of Visudyne-treated patients approximately 2
lines less than placebo-treated patients) to those observed in predominantly
classic lesions.
About Visudyne
Visudyne (verteporfin) is commercially available in over 60 countries for the
treatment of predominantly classic subfoveal CNV caused by AMD. It is also
approved in over 35 countries, including the EU, U.S. and Canada, for the
treatment of subfoveal CNV due to pathologic myopia (severe near-sightedness).
In the U.S., Visudyne has received an additional approval for CNV due to
presumed ocular histoplasmosis.
Visudyne therapy, developed by Novartis Ophthalmics and QLT Inc., is a two-step
procedure performed in a doctor's office. Visudyne is injected intravenously
into the patient's arm, and then a non-thermal laser light is shone into the
patient's eye to activate the treatment. Visudyne targets the abnormal blood
vessels while sparing overlying retinal cells. Multiple treatments are also a
vital element of the therapy course and current recommendations highlight them
as frequently as every three months if there is fluorescein leakage from CNV.
For more information, visit www.visudyne.com.
About AMD
AMD consists of two forms: wet and dry. Although only 15% of AMD patients suffer
from the wet form of the disease, this type is more aggressive and accounts for
approximately 500,000 new cases each year worldwide, and this estimate is
expected to grow dramatically as the population ages. AMD is caused by a growth
of abnormal blood vessels (CNV) under the central part of the retina or macula.
The vessels leak fluid and blood that lead to the development of scar tissue
that destroys the central retina. This results in a deterioration of sight over
a period of approximately two months to three years. "Occult" and "classic" are
terms used to describe the different patterns of CNV leakage as seen on
fluorescein angiography.
The foregoing press release contains forward-looking statements, relating to
Novartis' and QLT's business, respectively, that can be identified by
terminology such as "is key to maximising", "may help", "may have improved
benefits", "may be", "appeared potentially to be", or similar expressions. Such
forward-looking statements involve known and unknown risks, uncertainties and
other factors, which may cause the actual results and assumptions to be
materially different from any future results, performance or achievements
expressed or implied by such statements. Such factors include, but are not
limited to: risks associated with the development and commercialization of the
Visudyne treatment, including uncertainties relating to manufacturing, clinical
trials, registration, patient enrollment, pricing and reimbursement; patient and
physician demand for the treatment; competition; any uncertainty regarding
patents and proprietary rights; outcome of litigation claims, product liability
claims and insurance; government regulation; anti-takeover provisions;
dependence on corporate relationships; volatility of share prices; QLT Inc's
rapid growth, its history of operating losses and uncertainty of future
profitability, its access to capital; and any additional information and other
factors as described in detail in QLT Inc.'s Annual Information Form on Form
10-K and recent and forthcoming quarterly reports on Form
Page 13 of 35 Pages
10Q, Novartis AG's Form 20-F on file, and other filings with the US Securities
and Exchange Commission.
Background on Novartis Ophthalmics and QLT
Novartis Ophthalmics: With worldwide headquarters in Bulach, Switzerland,
Novartis Ophthalmics is a global leader in research, development and
manufacturing of leading ophthalmic pharmaceuticals that assist in the treatment
of glaucoma, age-related macular degeneration, eye inflammation, ocular
allergies and other diseases and disorders of the eye. Novartis Ophthalmics
products are available in more than 110 different countries. The North American
headquarters is based in Atlanta, Georgia. Novartis Ophthalmics has production
sites in Switzerland, France and Canada. For more information, visit
www.novartisophthalmics.com or www.novartisophthalmics.com/us.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
QLT Inc. (NASDAQ: QLTI; TSE:QLT) is a world leader in photodynamic therapy, a
field of medicine utilizing light-activated drugs in the treatment of disease.
QLT's innovative science has led to the development and commercialization of
breakthrough treatments utilizing this technology for applications in
ophthalmology and oncology and is exploring the potential in other diseases. For
more information, you are invited to visit QLT's web site at www.qltinc.com.
Dr. Bressler has been paid as a consultant to QLT Inc and Novartis Ophthalmics
but has no other potential conflict of interest. The terms of this agreement are
being managed by the Johns Hopkins University in accordance with its conflict of
interest policies.
# # #
Note to editors
MPS (Macular Photocoagulation Study) is a series of prospective, randomized
multicenter clinical trials funded by the US National Eye Institute to determine
the efficacy of laser photocoagulation in choroidal neovascularization caused by
age-related macular degeneration, ocular histoplasmosis and idiopathic causes.
Disc Area (DA) is the area of a circle with a diameter of 1500 microns equal to
1.77 mm squared in the macular photocoagulation study.
Page 14 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
--------------------------------------------------------------------------------
Novartis and QLT file new drug application in Japan, for Visudyne(R)
If approved, Visudyne could be highly beneficial to the patients losing central
vision
Basel, 23 April 2002 --Novartis Ophthalmics, the eye health unit of Novartis,
and QLT Inc. announced today the submission of a new drug application in Japan
for Visudyne(R) (verteporfin), a therapeutic treatment for AMD (age-related
macular degeneration) accompanied with subfoveal CNV-- a leading cause of
blindness in people over age 50.
Visudyne was developed as a therapeutic drug for the wet form of AMD following
its designation as an orphan drug in Japan in June 1997. The results of 6 month
clinical study which were presented at the international congress of
Ophthalmology in Sydney, have shown the excellent efficacy and safety of
Visudyne in Japanese AMD patients.
Visudyne therapy in approved countries is a two-step procedure involving the
intravenous administration of the drug and its followed laser application. This
therapy may subsequently cause selective destruction of neovascular tissue while
sparing overlying retinal cells. In Japan, Carl Zeiss Co Ltd., and Lumenis
Japan, Ltd. will submit pre-marketing approval applications shortly for laser
devices which would be used in Visudyne therapy, pending its approval.
Visudyne is commercially available in nearly 60 countries for the treatment of
certain types of predominantly classic subfoveal CNV caused by AMD. It is also
approved in over 35 countries, including the EU, U.S. and Canada, for the
treatment of subfoveal CNV due to pathologic myopia (severe near-sightedness).
In the U.S., Visudyne has received an additional approval for CNV due to
presumed ocular histoplasmosis. Over 150,000 patients have undergone Visudyne
therapy worldwide since its first launch in April 2000. If approved, Visudyne
could be highly beneficial to patients in Japan suffering from this devastating
eye disease that to date has no other effective therapy.
About AMD
AMD is the leading cause of blindness in people over the age of 50 and is caused
by a growth of abnormal blood vessels (CNV) under the central part of the retina
or macula. The vessels leak fluid and blood and can lead to the development of
scar tissue that destroys the central retina, resulting in a deterioration of
sight over a period ranging anywhere from two months to three years. Patients
with this disease ultimately lose their central vision, which is indispensable
for the activities of daily living including reading and driving. Although the
wet form (the form Visudyne is used to treat) represents an estimated 15% of all
AMD cases, it accounts for approximately 90%
Page 15 of 35 Pages
of the severe vision loss associated with the diseases. Worldwide, approximately
500,000 new cases of wet AMD occur each year and this estimate is expected to
grow dramatically as the population ages.
The foregoing press release contains forward-looking statements, relating to
Novartis' and QLT's business, respectively,that can be identified by terminology
such as "could be highly beneficial," or similar expressions. Such
forward-looking statements involve known and unknown risks, uncertainties and
other factors, which may cause the actual results and assumptions to be
materially different from any future results, performance or achievements
expressed or implied by such statements. Such factors include, but are not
limited to: risks associated with the development and commercialization of the
Visudyne treatment, including uncertainties relating to manufacturing, clinical
trials, registration, patient enrollment, pricing and reimbursement; patient and
physician demand for the treatment; competition; any uncertainty regarding
patents and proprietary rights; outcome of litigation claims, product liability
claims and insurance; government regulation; anti-takeover provisions;
dependence on corporate relationships; volatility of share prices; QLT Inc's
rapid growth, its history of operating losses and uncertainty of future
profitability, its access to capital; and any additional information and other
factors as described in detail in QLT Inc.'s Annual Information Form on Form
10-K and recent and forthcoming quarterly reports on Form 10Q, Novartis AG's
Form 20-F on file, and other filings with the US Securities and Exchange
Commission.
Background on Novartis Ophthalmics and QLT
Novartis Ophthalmics: With worldwide headquarters in Bulach, Switzerland,
Novartis Ophthalmics is a global leader in research, development and
manufacturing of leading ophthalmic pharmaceuticals that assist in the treatment
of glaucoma, age-related macular degeneration, eye inflammation, ocular
allergies and other diseases and disorders of the eye. Novartis Ophthalmics
products are available in more than 110 different countries. The North American
headquarters is based in Atlanta, Georgia. Novartis Ophthalmics has production
sites in Switzerland, France and Canada. For more information, visit
www.novartisophthalmics.com or www.novartisophthalmics.com/us.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
QLT Inc. (NASDAQ: QLTI; TSE:QLT) is a world leader in photodynamic therapy, a
field of medicine utilizing light-activated drugs in the treatment of disease.
QLT's innovative science has led to the development and commercialization of
breakthrough treatments utilizing this technology for applications in
ophthalmology and oncology and is exploring the potential in other diseases. For
more information, you are invited to visit QLT's web site at www.qltinc.com.
# # #
Page 16 of 35 Pages
Investor Relations Novartis International AG
[NOVARTIS LOGO] CH-4002 Basel
Switzerland
Karen J Huebscher, PH.D.
Tel +41 61 324 8433
Nafida Bendali
Tel +41 61 324 3514
Sabine Moravi, MBA
Tel + 41 61 324 8989
Silke Zenter
Tel +41 61 324 8612
Francisco Bouzas
Tel +41 61 324 8444
Fax + 41 61 324 8844
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
- Investor Relations Release -
--------------------------------------------------------------------------------
Exciting data suggest that adding entacapone from the first dose of levodopa
therapy may delay the emergence of dyskinesia in Parkinson's disease
Basel, 19 April, 2002 - Important new evidence in Parkinson's disease now shows
that entacapone in combination with levodopa can provide a more continuous,
physiological stimulation of the dopamine receptors, which not only rapidly
improves symptom control, but can also significantly reduce the development of
dyskinesia in the long-term. Levodopa (L-DOPA) is deservedly the mainstay and
most effective Parkinson's disease treatment. However, when used long-term,
current levodopa therapy can be associated with the development of motor
complications, including dyskinesias and wearing-off phenomena. The new data,
presented for the first time at the American Academy of Neurology (AAN)
congress, Denver, Colorado, demonstrate the potential of this
levodopa/entacapone combination for the effective long-term management of
Parkinson's disease patients from treatment initiation. Entacapone extends the
half life of each levodopa dose and ensures a more continuous delivery of
dopamine.
Recent findings using a primate model of Parkinson's disease have shown that,
compared with levodopa alone, co-administration of entacapone with levodopa not
only enhances parkinsonian symptom control by consistently improving daily
locomotor activity, but, in the long-term, also avoids the induction of
dyskinesias. MPTP-treated primates were used as the animal model of choice
because the dyskinesias that occur in these animals following chronic
intermittent administration of levodopa closely resemble those observed in
clinical Parkinson's disease.
Commenting on the clinical relevance of these data, its author, Professor Peter
Jenner, Director of the Neurodegenerative Diseases Research Centre, of King's
College London said "We have shown for the first time that by providing a more
continuous stimulation of striatal dopamine receptors, the combination of
levodopa and entacapone has the potential to avoid the development of
dyskinesias. This supports the notion that levodopa continuous dopaminergic
stimulation is important for preventing the priming effect that underlies
involuntary movements in Parkinson's disease".
Physicians are increasingly concerned that long-term, non-physiological
pulsatile stimulation of dopamine receptors with standard levodopa formulations
or with other short acting dopaminergic therapies may, at least in part, be
responsible for the development of dyskinesias, as well as motor fluctuations.
The present data strongly suggest that administration of the levodopa/entacapone
Page 17 of 35 Pages
combination, currently used to treat fluctuating patients who are experiencing
wearing-off, may provide an effective means of treating Parkinson's disease from
the early stages of the disease, with the potential to avoid the induction of
motor complications in the long-term. Orion Pharma and Novartis are undertaking
clinical studies to verify that these results are also seen in Parkinson's
disease patients. One study has already been initiated with de-novo patients,
which will aim to highlight symptomatic benefits.
The foregoing press release contains forward-looking statements which can be
identified by terminology such as "exciting data suggest", "can provide", "can
also significantly reduce", "potential", "effective long-term management",
"consistently improving", "strongly suggest that," "may provide" or similar
expressions. Such forward looking statements involve known and unknown risks,
uncertainties and other factors that may cause the actual results to be
materially different from any future results, performance, or achievements
expressed or implied by such statements. Commercialization of entacapone can be
affected by, amongst other things, uncertainties relating to product
development, regulatory actions or delays or government regulation generally,
the ability to obtain or maintain patent or other proprietary intellectual
property protection and competition in general, as well as factors discussed in
the Company's Form 20-F filed with the US Securities and Exchange Commission.
Should one or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary materially from
those described herein as anticipated, believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
Orion Pharma is a research and development-orientated pharmaceutical division of
the Orion Group. The Orion Group (HEX:ORI) is one of the leading companies in
the healthcare sector in the Nordic area of Europe. The 2001 net sales of the
Group were EUR 970.8 million. The Orion Group employs around 5,371 people.
Pharmaceutical R&D at Orion Pharma produce new innovative drugs in four core
therapy areas: CNS therapies, cardiology and critical care, hormonal therapies,
and respiratory therapies. Entacapone, a COMT enzyme inhibitor, is Orion
Pharma's patented molecule discovery, which Orion Pharma developed through
multinational clinical trials. Entacapone is available globally as Comtess and
Comtan. For further information please consult http://www.orion.fi.
# # #
Page 18 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
--------------------------------------------------------------------------------
Novartis addresses ethical challenges of stem cell research
Global research guidelines issued for the first time by a pharmaceutical company
- compliance to be monitored by newly established Ethics Committee
Basel, 18 April 2002 - Novartis has established an Ethics Committee for research
on human stem cells, which is to be chaired by ethics Professor Hans-Peter
Schreiber of the Swiss Federal Institute of Technology (ETH), Zurich. The
interdisciplinary six-member body is to monitor global compliance with the
company's internal ethical guidelines.
According to these guidelines, the use of embryonic stem cells in research is
only considered to be justified if they derive from surplus embryos created by
in vitro fertilization procedures or from aborted fetuses. It is, however,
essential that fertilization should have taken place for reproductive purposes.
In addition, parents need to give their consent to the use of the cells for
research purposes, and they are not permitted to benefit financially. It must
also be demonstrated that the embryos concerned are no longer intended to be
implanted into the mother.
The creation of human embryos purely for research purposes would not be
compatible with these guidelines. Therapeutic cloning is also ruled out, as this
technique currently involves serious risks, as well as raising a wide variety of
ethical concerns.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 19 of 35 Pages
Investor Relations Novartis International AG
[NOVARTIS LOGO] CH-4002 Basel
Switzerland
Karen J Huebscher, PH.D.
Tel +41 61 324 8433
Nafida Bendali
Tel +41 61 324 3514
Sabine Moravi, MBA
Tel + 41 61 324 8989
Silke Zenter
Tel +41 61 324 8612
Francisco Bouzas
Tel +41 61 324 8444
Fax + 41 61 324 8844
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
- Investor Relations Release -
--------------------------------------------------------------------------------
Novartis drug Glivec(R)now also approved in Switzerland for treatment of
life-threatening kind of gastrointestinal cancer
Second approval in less than a year for Glivec(R) in Switzerland: in addition to
chronic myeloid leukemia indication, Glivec can now also be used in
gastrointestinal stromal tumors, representing a promising breakthrough in the
field of solid tumors.
Basel, 15 April 2002 - Swissmedic, the Swiss health authority, has given the
Novartis drug Glivec(R) (imatinib)(1) approval for the treatment of adult
patients with unresectable and/or metastatic malignant gastrointestinal stromal
tumors (GISTs). Prior to the availability of Glivec, patients had no effective
treatment options beyond surgery.
"Glivec already has dramatically improved the lives of many patients with CML,
and we are extremely glad that we are now also able to offer this medicine to
patients with GISTs," commented Dr. Daniel Vasella, Chairman and CEO of
Novartis. "Together with our colleagues in the academic and state sectors,
Novartis is conducting further studies with Glivec and also investigating other
forms of cancer where Glivec could help patients - either as monotherapy or in
combination with other treatments."
Last year, Glivec had already received a great deal of attention and acclaim due
to its efficacy in the treatment of chronic myeloid leukemia (CML) in the blast
crisis, accelerated phase or in chronic phase after failure of interferon-alpha
therapy. The drug's mechanism of action, involving selective inhibition of
enzymes (so-called tyrosine kinases) that are responsible for growth of certain
tumors, prompted efforts to investigate the use of Glivec in additional
indications - including solid tumors.
Glivec was approved for the GIST indication in the US in February 2002, and a
positive opinion also has been received from the Committee for Proprietary
Medicinal Products (CPMP) in Europe.
What are GISTs?
GISTs are the most common malignant form of sarcoma that arise in the
gastrointestinal tract, predominantly affecting middle-aged patients. Worldwide,
there are approximately 12,000 new cases each year.
----------
(1) In the US:Gleevec(TM) (imatinib mesylate); outside the US: Glivec(R)
(imatinib)
Page 20 of 35 Pages
Historically, GISTs have been very difficult to treat due to their high levels
of resistance to treatment with traditional chemotherapy and radiation therapy.
For patients with metastatic or unresectable disease, GISTs had represented an
incurable malignancy, with a median survival of approximately one year. In cases
where surgery was possible, it resulted essentially in palliation of the
disease. For these patients, Glivec now offers a revolutionary treatment option,
which has displayed exceptional results in clinical trials: in a majority of
patients, Glivec produced dramatic tumor regression.
About Glivec and GISTs
In February 2002, the Committee for Proprietary Medicinal Products (CPMP) gave a
positive opinion for the GIST indication which is supported by data from an
open-label, multinational study conducted in 147 patients with unresectable or
metastatic malignant GISTs. Patients were randomized to receive either 400 mg or
600 mg of Glivec daily for up to 24 months. The overall response rate was 40%,
based on confirmed partial responses at the time of the data cut-off for the
submission.
About Glivec and CML
In Switzerland, Glivec received approval in June 2001 for the CML indication,
i.e., for the treatment of patients in blast crisis, accelerated phase or in
chronic phase after failure of interferon-alpha therapy. It is also approved for
use in this indication in the US and the EU, and in more than 60 other
countries.
Newly-Diagnosed CML Patients
In regards to newly-diagnosed CML patients, data presented at the 2001 meeting
of the American Society of Hematology showed that use of Glivec in the early
chronic phase can result in higher cytogenetic response rates. After three
months of treatment, 77% had achieved complete or major cytogenetic responses
(Ph<35%). The hematological response rate was 98%. In comparison, in previously
reported studies of other agents (interferon-alpha alone and interferon-alpha
with Ara-C and homoharringtonine), 2-24% of patients on other treatments
achieved complete or major cytogenetic responses after three months of
treatment.
In a large ongoing Phase III study (IRIS, International Randomized study of
Interferon vs. STI571), Glivec is being evaluated vs. the combination of
standard interferon and cytarabine as first line therapy in patients with
chronic myeloid leukemia. An interim analysis of this ongoing study showed that
the Glivec arm demonstrated early on a substantially higher response. Based on
this finding, the Independent Data Monitoring Board (IDMB) recommended a change
in the protocol to enable the patients on standard therapy who have not achieved
a major cytogenetic response to switch to Glivec at this time.
An update of these data will be presented at a plenary session at the 2002
congress of the American Society of Clinical Oncology (ASCO), Orlando, Florida,
16-21 May.
Contraindications and adverse events
Although the majority of patients had adverse events reported at least once
during the trial, most events were mild to moderate in severity. In the GIST
trial, drug was discontinued for adverse events in six patients (8%) in both
dose levels studied. In this clinical trial, the most common adverse events were
edema, nausea, diarrhea, abdominal pain, muscle cramps, fatigue and rash. In
this trial, seven patients (5%) were reported to have gastrointestinal bleeds
and/or intratumoral bleeds. Gastrointestinal tumor sites may have been the
source of GI bleeds. Glivec is
Page 21 of 35 Pages
contraindicated in patients with known hypersensitivity. Women of childbearing
potential should be advised to avoid becoming pregnant while taking Glivec.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "can now also be used," "promising breakthrough," "for
the first time," "offers a revolutionary treatment option," "exceptional
results," "dramatic tumor regression," "dramatically improved" or similar
expressions. Such forward-looking statements involve known and unknown risks,
uncertainties and other factors that may cause actual results with Glivec to be
materially different from any future results, performance or achievements
expressed or implied by such statements. In particular, management's ability to
ensure satisfaction of the FDA's further requirements is not guaranteed and
management's expectations regarding further commercialization of Glivec could be
affected by, among other things, additional analysis of data; new data;
unexpected clinical trial results; unexpected regulatory actions or delays or
government regulation generally; the Company's ability to obtain or maintain
patent or other proprietary intellectual property protection; competition in
general; and other risks and factors referred to in the Company's current Form
20-F on file with the Securities and Exchange Commission of the United States.
Should one or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary materially from
those anticipated, believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 22 of 35 Pages
Investor Relations Novartis International AG
[NOVARTIS LOGO] CH-4002 Basel
Switzerland
Karen J Huebscher, PH.D.
Tel +41 61 324 8433
Nafida Bendali
Tel +41 61 324 3514
Sabine Moravi, MBA
Tel + 41 61 324 8989
Silke Zenter
Tel +41 61 324 8612
Francisco Bouzas
Tel +41 61 324 8444
Fax + 41 61 324 8844
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
- Investor Relations Release -
--------------------------------------------------------------------------------
New immunosuppressant CerticanTM addresses a key risk factor in late graft loss
- First ever clinical data for an immunosuppressant to show a significant
reduction in vasculopathy
Basel, Switzerland, 12 April 2002 - New clinical data on the investigational
transplantation drug CerticanTM (everolimus), a proliferation inhibitor,
presented at the International Society of Heart and Lung Transplantation (ISHLT)
in Washington, demonstrate a significant reduction in acute rejection and graft
vasculopathy (proliferation of smooth muscle cells in the intima - or innermost
wall - of the graft vessels, leading to gradual thickening, vessel narrowing and
restriction of blood supply). This is the first time that an immunosuppressant
has been shown to significantly reduce vasculopathy.
"After one year vasculopathy is the most serious risk-factor for long-term graft
loss," commented Professor Jon Kobashigawa MD, University of California, Los
Angeles one of the investigators of the study. "Late graft loss is a critical
issue, and one that traditional immunosuppressants have failed to control
adequately. A major challenge in transplantation is to improve long-term graft
survival," he added, "Our hope is that the benefit of reduced vasculopathy at 12
months will translate into long-term benefits."
In this international trial, 634 heart transplant patients (all receiving
Neoral(R) - cyclosporin microemulsion - and steroids) were randomised to one of
three groups: Certican at 1.5 mg/day, Certican at 3.0 mg /day or to the standard
add-on immunosuppressant therapy azathioprine at 1-3 mg/kg/day.
Acute rejection rates after 12 months were significantly lower (p<0.001) in
patients receiving Certican at 3.0 mg/day (21.3%), than in patients on
azathioprine at 1-3 mg/kg/day (45.8%). In patients given Certican at 1.5mg/day
the acute rejection rate was 30.6%, compared with 45.8% with azathioprine
(p<0.001).
Of particular importance, 12 months data showed that the addition of Certican to
the standard regimen significantly (p <0.05) lowered the incidence of graft
vasculopathy compared with azathioprine. Vasculopathy was measured serially
using a specialised, state-of-the-art intravascular ultrasound (IVUS) technique
to measure the thickness of the intima of the vessel.
Page 23 of 35 Pages
In addition to acute rejection rates and intimal thickening being significantly
lower in the Certican group than in the azathioprine group, the study also
showed a significant reduction (p<0.001) in the incidence of cytomegalovirus
(CMV) infections, which is an important risk factor for the development of
vasculopathy.
The investigators concluded that these attributes of Certican could conceivably
have a major impact both on the health-related quality of life of heart and
other transplant patients as well as on medical care resource utilisation - by
decreasing morbidity, graft loss and costs of prolonged hospitalisation and/or
re-transplantation.
This international trial is planned to run for another year.
About Rejection:
Acute rejection, which is usually an immune mediated reaction occurs within days
to weeks following a transplant. Chronic, or long-term rejection rejection,
which occurs months to years after a transplant, is usually the result of immune
and non-immunological mechanisms.
About Certican:
Described as a 'Proliferation Inhibitor', Certican is being evaluated for
co-administration with Neoral(R) and appears to target primary causes of chronic
rejection.
Certican is in phase III development {renal, heart and lung transplantation}.
The licence application is for use in both kidney and heart transplantation.
About Neoral(R):
Neoral(R) (cyclosporin microemulsion) is the cornerstone of immunosuppression in
transplant patients, permitting long-term survival, but the risk of acute and
chronic graft rejection persists. Identifying additional immunosuppressive
agents - which can act in combination with Neoral(R) to further maximise patient
outcomes - is therefore a priority in transplantation research.
Further Details of the Study:
The primary endpoint was all-cause efficacy failure: acute rejection episode
(above a specified severity level), graft loss / re-transplant, death or loss to
follow up (i.e. a composite endpoint). Secondary endpoints included all of these
eventualities measured separately. The trial was robustly designed, being a
randomised, double-blind, double-dummy, parallel group study.
Intimal width was measured by serial intravascular ultrasound (IVUS) undertaken
1-6 weeks after transplantation and one year later. Graft vasculopathy was
defined as at least a 0.5mm increase from baseline in maximum intimal thickness.
This release contains certain 'forward-looking statements', relating to the
Company's business, which can be identified by the use of forward-looking
terminology such as 'planned to', 'conceivable', 'could have', 'is due to be' or
similar expressions, or by discussions regarding the potential development of
new products. Such statements reflect the current views of the Company with
respect to future events and are subject to certain risks, uncertainties and
assumptions. Many factors could cause the actual results, performance or
achievements of the Company to be materially different from any future results,
performances or achievements that may be expressed or implied by such
forward-looking statements. There are no guarantees that any new products will
be commercialised in any market. Any such commercialisation can be affected by,
among other things, uncertainties relating to product development and clinical
trials, regulatory actions or
Page 24 of 35 Pages
delays or government regulation generally, the ability to obtain or maintain
patent or other proprietary intellectual property protection and competition in
general,as well as factors discussed in the Company's Form 20F filed with the
Securities and Exchange Commission. Should one or more of these risks or
uncertainties materialise, or should underlying assumptions prove incorrect,
actual results may vary materially from those described herein as anticipated,
believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 25 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
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Novartis researchers honored by American Association for Cancer Research for
discovery work on Glivec(R)
Bruce F. Cain Memorial Award honors outstanding preclinical research on novel
drug that has implications for the improved care of cancer patients
Basel, 9 April 2002 - Alex Matter, MD, Therapeutic Area Head of Oncology
Research at Novartis Oncology is one of four recipients of the annual Bruce F.
Cain Award for their discovery and preclinical work on Glivec(R) (imatinib)2.
Glivec is an oral drug that has shown unprecedented efficacy in the treatment of
certain forms of leukemia and gastrointestinal tumors. The annual award from the
American Association for Cancer Research (AACR) was bestowed at the 2002 meeting
held in San Francisco, California.
"I am most pleased that our oncology research team under the outstanding
leadership of Alex Matter has been able to bring a breakthrough medicine such as
Glivec to patients, and that this work has been recognized with the AACR award.
The commitment and concern for those who were desperately ill inspired the
team's pioneering work, which is a hallmark of how rational drug design and the
pharmaceutical industry will contribute to future medical therapy", said Daniel
Vasella, MD, Chairman and CEO, Novartis. "Under Alex Matter's guidance, and with
our strength in signal transduction and tyrosine kinase inhibition, Novartis can
look forward to future discoveries which will advance the oncology field."
Dr. Matter will share the prize with his co-awardees - Elisabeth Buchdunger,
Ph.D., from Preclinical Research; Jurg Zimmermann, Ph.D., Head of Combinatorial
Chemistry; and Nicholas B. Lydon, Ph.D., formerly with the oncology research
team at Ciba-Geigy (now Novartis) and now Vice President for Small Molecule Drug
Discovery, Amgen, Inc.
The award was established in 1982 by the AACR and the Warner-Lambert Company
(now Pfizer) to honor the memory of Dr. Bruce F. Cain of New Zealand for his
work in the design, synthesis, and biological evaluation of potential anticancer
drugs. The purpose of the award is to give recognition to an individual or
research team for outstanding preclinical research that has implications for the
improved care of cancer patients.
"I am honored to accept this award on behalf of the team at Novartis that
discovered Glivec," said Dr. Matter. "Glivec is helping thousands of cancer
patients each year, and being involved in the discovery and development of this
drug has been a once-in-a-lifetime opportunity for everyone involved."
1 In the US: Gleevec(TM)(imatinib mesylate); outside the US: Glivec(R)(imatinib)
Page 26 of 35 Pages
About Dr. Matter and The Discovery of Bcr-Abl
Dr. Matter began building a cancer research unit focused primarily on inhibition
of kinases (Bcr-Abl is one) in 1983, when he headed the research team at the
company Ciba-Geigy (now Novartis) in Basel, Switzerland. By early 1990, Dr.
Matter and his team, including all of the award co-winners, discovered Bcr-Abl
inhibitors and focused their efforts on one particularly promising compound,
which eventually became Glivec.
Dr. Matter received his medical degrees from the Universities of Basel and
Geneva, and completed his doctoral thesis at the Institute of Pathology at the
University of Basel. He held fellowships at the Swiss National Science
Foundation and the Swiss Academy for Medical Sciences. He currently holds
teaching positions at the University of Basel and the European University
Confederation of Rhine (EUCOR) and has been an invited lecturer for numerous
conferences including the European Oncology Spring Conference, International
Union Against Cancer (UICC) and Conferences on Cancer, the American Association
for Cancer Research (AACR) Meeting. Dr. Matter has published more than 100
scientific articles plus several book chapters in the area of oncology and
hematology. Together with a team of Glivec pioneers, in 2001 he won the
prestigious Alpert Foundation Scientific Prize administered by Harvard
University, as well as the Novartis Excellence Award for Innovation.
Glivec to Date
The Phase I study with Glivec began in June 1998. The initial results were
extremely promising and the company devoted significant resources to accelerate
the compound's development. In February 2001, a new drug application was filed
with health authorities globally - only 32 months after initiation of the Phase
I trial. On May 10, two and one-half months later, Glivec was approved by the
U.S. Food and Drug Administration for the treatment of patients with
Philadelphia chromosome positive chronic myeloid leukemia in the blast crisis,
accelerated phase or in chronic phase after failure of interferon-alpha therapy.
This marked the fastest cancer drug approval by the Agency. Today, it is
approved in more than 60 countries for this indication. In February 2002, Glivec
was approved by the FDA for the treatment of patients with Kit (CD 117) positive
unresectable (inoperable) and/or metastatic malignant gastrointestinal stromal
tumors (GISTs). Also in February of this year, Novartis received a positive
opinion from the Committee for Proprietary Medicinal Products (CPMP) for use of
Glivec in treating patients with GIST.
Contraindications and Adverse Events
The majority of patients treated with Glivec experience adverse events at some
time. In the CML studies, the most common side effects include nausea, vomiting,
abdominal pain, dyspepsia, diarrhea, edema and fluid retention, rash, muscle
cramps, fatigue and headache, as well as neutropenia, thrombocytopenia and
hemorrhage. Most events are of mild to moderate grade. Events, such as
hepatotoxicity, fluid retention syndrome, neutropenia and thrombocytopenia may
be serious and severe. Women of childbearing potential should be advised to
avoid becoming pregnant while taking Glivec.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "unprecedented efficacy", "extremely promising" or
similar expressions. Such forward-looking statements involve known and unknown
risks, uncertainties and other factors that may cause actual results with Glivec
to be materially different from any future results, performance or achievements
expressed or implied by such statements. In particular, management's ability to
ensure satisfaction of the FDA's further requirements is not guaranteed and
management's expectations regarding further commercialization of Glivec could be
affected by, among other
Page 27 of 35 Pages
things, additional analysis of data; new data; unexpected clinical trial results
for Glivec; unexpected regulatory actions or delays or government regulation
generally; the Company's ability to obtain or maintain patent or other
proprietary intellectual property protection; competition in general; and other
risks and factors referred to in the Company's current Form 20-F on file with
the Securities and Exchange Commission of the United States. Should one or more
of these risks or uncertainties materialize, or should underlying assumptions
prove incorrect, actual results may vary materially from those anticipated,
believed, estimated or expected.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 28 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
--------------------------------------------------------------------------------
Novartis launches world's smallest ERT patch in Germany - its first major
European market
Basel, 9 April 2002 - Novartis announced today it has launched its one-of-a-kind
DOT Matrix(TM) estrogen replacement therapy patch, Estradot(R)
(17(beta)-estradiol), for the treatment of menopausal symptoms in Germany. This
is the first major European market to launch the product, where research shows
nearly 40% of the women over the age of 45 are going through menopause - many
with symptoms such as hot flushes, night sweats and mood swings.
"Estradot really is going to shape the future for the Novartis HRT portfolio,"
said Kees Roks, Therapeutic Area Head, Germany, "Our use of the innovative and
advanced DOT Matrix(TM) Technology will enable Novartis to help women worldwide
get effective relief from their menopausal symptoms."
About Estradot "The Tiny Patch"
Estradot is the first estrogen patch available in Europe using Noven's DOT
Matrix(TM) technology licensed by Novartis. This innovative technology has made
it possible to manufacture Estradot, the smallest estrogen replacement therapy
(ERT) patch in the world - the size of a postage stamp.
DOT Matrix(TM) is a new class of drug-in-adhesive transdermal patch technology
that delivers a therapeutic dose of drug through a small patch area without
compromising comfort or adhesion. DOT Matrix(TM) makes Estradot the smallest,
most efficient transdermal estrogen patch available. Because of this patented
technology, Estradot carries only a fraction of the drug contained in other
patches, but delivers a much greater percentage of that drug into the system.
So, less drug = smaller size = high efficiency.
Estradot has also been shown in scientific studies to have excellent adhesion,
tolerability and almost no skin irritation. It will also stay put when
showering, swimming, sweating and during most daily activities.
Estradot's delivery system bypasses the 1st pass metabolism. Mimicking the
process of ovarian secretion, the hormone is released in low doses directly into
the systemic circulation, using less than one tenth the dose of
orally-administered estrogen to achive therapeutic blood serum concentrations
With Estradot, women can rest assured they are receiving natural
17(beta)-estradiol derived from the soya plant, which mimics the exact
physiologic estrogen a woman produces during her premenopausal years.
Page 29 of 35 Pages
Estradot, the "Tiny Patch", is appealing to many women because its very easy to
use, comfortable and discreet. This enhances compliance, thus providing women
long-term relief from their menopausal symptoms, which are often debilitating.
Estradot is available in four flexible doses: 37.5, 50, 75 and 100 mcg, and is
changed twice a week.
About Menopause
The natural transition to menopause normally occurs around age 45 with the
gradual cessation of ovarian function. Although this is considered as a natural
phenomenon in every woman's life, it can, however, give rise to unpleasant
climacteric symptoms such as hot flushes, night sweats, vaginal dryness, low
libido, mood swings and/or depression, as well as urogenital atrophy and
osteoporosis. These consequences of estrogen deficiency can also lead to a
deterioration in quality of life. The aim of hormone replacement therapy (HRT)
is to eliminate climacteric symptoms, to prevent premature disease and
disability, and thus improve women's health.
This press release contains forward looking statements which can be identified
by the use of forward-looking terminology such as "will now get relief", "can
rest assured", "appealing to many women", "enhances compliance", "long-term
relief"or similar expressions. Such forward looking statements involve known and
unknown risks, uncertainties and other factors that may cause actual results to
be materially different from any future results, performance or achievements
expressed or implied by such statements. Any commercialisation can be affected
by, amongst other things, uncertainties relating to product development,
regulatory actions or delays or government regulation generally, the ability to
obtain or maintain patent or other proprietary intellectual property protection
and competition in general, as well as factors discussed in Novartis AG's Form
20F filed with the Securities and Exchange Commission. Any of these and other
factors can cause the actual results to differ materially from the expected or
predicted results.
DOT Matrix(TM)is a patented technology of Noven Pharmaceuticals, Inc. (Nasdaq:
NOVN).
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
Page 30 of 35 Pages
Investor Relations Novartis International AG
[NOVARTIS LOGO] CH-4002 Basel
Switzerland
Karen J Huebscher, PH.D.
Tel +41 61 324 8433
Nafida Bendali
Tel +41 61 324 3514
Sabine Moravi, MBA
Tel + 41 61 324 8989
Silke Zenter
Tel +41 61 324 8612
Francisco Bouzas
Tel +41 61 324 8444
Fax + 41 61 324 8844
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
- Investor Relations Release -
--------------------------------------------------------------------------------
Studies show long-term benefits of Exelon(R)(rivastigmine) in Alzheimer's
disease
Effectiveness demonstrated for at least two years, when other therapies often
fail
Basel, Switzerland, 5 April 2002 - Exelon(R) (rivastigmine) provides sustained
benefits for people with Alzheimer's disease for at least two years, according
to a large multicenter data analysis presented today at the Seventh
International Geneva/Springfield Symposium on Advances in Alzheimer's
Therapy(1). The report included data from the longest studies conducted to date
on Exelon, and showed the drug slowed cognitive decline compared to placebo or
no treatment for up to two years. Exelon is currently approved for treatment of
mild to moderate Alzheimer's disease.
"These are important results because they are the first to confirm the benefits
of Exelon over such a long period of time and in a large number of patients,"
said George Grossberg, MD, lead author of the report and Director of Geriatric
Psychiatry at Saint Louis University School of Medicine in St. Louis, Missouri,
USA. "The finding of a sustained benefit is good news for individuals with
Alzheimer's disease and for the physicians and family members who care for
them," he said.
Although its exact causes are not understood, Alzheimer's disease (AD) is
associated with decreased transmission of signals between nerves in the brain,
especially those that rely on the neurotransmitter acetylcholine. Exelon is
unique because it treats AD by inhibiting the two key enzymes involved in
breaking down acetylcholine - acetylcholinesterase and butyrylcholinesterase -
thus preventing the breakdown of the neurotransmitter and prolonging its action.
Other drugs commonly used to treat AD, such as donepezil and galantamine,
inhibit acetylcholinesterase but not butyrylcholinesterase. Recent research
suggests that butyrylcholinesterase may play an increasingly important role in
regulating acetylcholine levels as AD progresses, and that the dual inhibitory
action of Exelon may provide greater and more sustained efficacy in treating
patients with the disorder.(2)
Analysis and findings
For the analysis, the cognitive performance of 2010 Exelon-treated patients from
113 centers in the U.S. and other countries was compared both to their projected
performance if they were untreated and to published data of patients treated
with a placebo. Data on Exelon patients were from open-label extension studies
of four six-month, randomized, placebo-controlled trials. During the
Page 31 of 35 Pages
extension studies, patients received from 1 to 6 mg Exelon twice daily, within
the recommended range. Standardized tests were used to measure patients'
cognitive performance and the clinician's overall assessment of the patients'
condition.(3)
Exelon treatment resulted in less cognitive deterioration than projected for
untreated or placebo-treated patients. For example, after two years, scores of
cognitive function (ADAS-Cog scale, 0 to 70 point range) for Exelon patients
deteriorated an average of 5 points less than projected for untreated patients
(8.6 vs. 13.6 points, respectively). The lower rate of cognitive decline was
determined to be clinically relevant, as shown by smaller-than-expected declines
in clinicians' assessments of the patients' global functioning.
About Alzheimer's disease
Alzheimer's disease (AD) is a progressive, degenerative disease that alters the
brain, causing impaired memory, thinking and behaviour. Affecting approximately
15 million people worldwide and 5 to 10 percent of those over 65 years of age,
it is the most common form of dementia and the leading cause of death behind
cardiovascular disease and cancer.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
1 Grossberg G, Spiegel R, Satlin A, Mesenbrink P. Rivastigmine in
Alzheimer's disease: efficacy over two years. Abstract 33A. Presented
at: The Seventh International Geneva/Springfield Symposium on Advances
in Alzheimer's Therapy, Geneva Switzerland, April 4, 2002.
2 Ballard CG. Advances in the treatment of Alzheimer's disease: benefits
of dual cholinesterase inhibition. Eur Neurol 2002; 47(1):64-70.
3 Cognitive performance was assessed by the Alzheimer Disease Assessment
Scale - Cognitive subscale and the Mini-Mental State Examination;
clinical relevance of the changes observed were assessed by the
Clinician Interview-Based Impression of Change (CIBC-Plus), the Global
Deterioration Scale (GDS), and the Progressive Deterioration Scale
(PDS).
Page 32 of 35 Pages
Novartis International AG
[NOVARTIS LOGO] Novartis Communications
CH-4002 Basel
Switzerland
Tel +41 61 324 2200
Fax + 41 61 324 3300
Internet Address:
http://www.novartis.com
--------------------------------------------------------------------------------
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
--------------------------------------------------------------------------------
Study shows Elidel(R) Cream 1% significantly improves eczema signs and symptoms
in patients with mild to moderate disease
Data highlight Elidel efficacy in treating head and neck eczema
Basel, 2 April 2002 - Elidel(R) (pimecrolimus) Cream 1% significantly improves
the signs and symptoms of atopic eczema, particularly in the head and neck
regions. These data are published in the April issue of the Journal of the
American Academy of Dermatology. Elidel, a new non-steroid prescription cream
for the treatment of atopic eczema (also known as atopic dermatitis) in patients
as young as 3 months of age, was approved in Denmark last month.
"Traditionally it's been difficult to treat the head and neck regions due to
concerns over side effects with using corticosteroids on these sensitive areas.
These data underscore the safety and efficacy of using Elidel on these most
sensitive skin areas," said Dr. Lawrence Eichenfield, Chief of Pediatric and
Adolescent Dermatology, Children's Hospital, San Diego, USA, and lead author of
the study. "Having a well-tolerated, steroid-free treatment available that can
be safely used on all skin surfaces is an important advance in the treatment of
this disease."
The analysis from pooled results of two independent, identically designed,
six-week, randomized, multi-center studies involving a total of 403 patients,
showed significant improvement in the signs and symptoms of eczema in
Elidel-treated patients, particularly in the head and neck regions, versus
placebo cream. As measured by the Eczema Area and Severity Index (EASI), head
and neck eczema in the Elidel-treated patients improved by more than 40-percent
on average by day eight and nearly 60-percent on average by conclusion of the
study. This compared with no improvement at the conclusion of the study for
those using placebo cream.
Elidel had a significant effect on pruritus (itching), with nearly 45-percent of
patients reporting no to mild itching within the first week of treatment,
compared to approximately 26-percent of patients on placebo treatment.
About Elidel
Discovered by the Novartis Research Institute in Vienna, Austria, Elidel was
officially launched in its first market, the US, last month for the treatment of
mild to moderate atopic eczema in patients aged two years and older. Also last
month Elidel gained its first European approval, in Denmark, where it is
indicated for the short term treatment of the signs and symptoms of atopic
eczema and intermittent long-term treatment to prevent progression to flares in
patients 3 months of age and above. It is approved for use in patients in whom
conventional topical corticosteroid therapy is not advisable because of
potential risks or in patients who are not adequately responsive to, or are
Page 33 of 35 Pages
intolerant of, conventional topical corticosteroid therapy. Elidel is expected
to be available in Denmark around mid-year.
Novartis will seek approvals in other European countries during 2002 under the
Mutual Recognition Procedure, and has filed for approval in other countries
worldwide.
Approvals of Elidel have been based on safety and efficacy results of clinical
trials in more than 1800 pediatric and adult patients with atopic eczema. The
most common side effect on the skin was a mild to moderate, temporary feeling of
warmth or burning (occurring in 8-percent of children age two to 17 and in
26-percent of adults). Other common side effects included headache and cold-like
symptoms. Elidel did not induce contact sensitization, phototoxicity or
photoallergy, nor did it show any cumulative irritation. Elidel did not elicit
skin atrophy like that from topical corticosteroid use.
The active ingredient is pimecrolimus, which is derived from ascomycin, a
natural substance produced by the fungus Streptomyces hygroscopicus var.
ascomyceticus. Pimecrolimus selectively blocks the production and release of
cytokines from T-cells. It is these cytokines which trigger processes leading to
the inflammation, redness and itching associated with eczema.
This press release contains forward looking statements which can be identified
by the use of forward-looking terminology such as "will seek approvals", "is
expected," or similar expressions. Such forward looking statements involve known
and unknown risks, uncertainties and other factors that may cause actual results
to be materially different from any future results, performance or achievements
expressed or implied by such statements. There are no guarantees that the
aforementioned data, clinical trials and regulatory approvals will result in the
commercialisation of Elidel cream in any market. Any such commercialisation can
be affected by, amongst other things, uncertainties relating to product
development, regulatory actions or delays or government regulation generally,
the ability to obtain or maintain patent or other proprietary intellectual
property protection and competition in general, as well as factors discussed in
Novartis AG's Form 20F filed with the US Securities and Exchange Commission. Any
of these and other factors can cause the actual results to differ materially
from the expected or predicted results.
Novartis AG (NYSE: NVS) is a world leader in healthcare with core businesses in
pharmaceuticals, consumer health, generics, eye-care, and animal health. In
2001, the Group's businesses achieved sales of CHF 32.0 billion (USD 19.1
billion) and a net income of CHF 7.0 billion (USD 4.2 billion). The Group
invested approximately CHF 4.2 billion (USD 2.5 billion) in R&D. Headquartered
in Basel, Switzerland, Novartis Group companies employ about 71,000 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
Page 34 of 35 Pages
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf by the
undersigned, thereunto duly authorized.
Novartis AG
Date: May 2, 2002 By: /s/ RAYMUND BREU
-------------------------
Name: Raymund Breu
Title: Chief Financial Officer
Page 35 of 35 Pages