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 May 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 Drug Glivec(R)(imatinib)* Approved in European Union for
Treatment of Life-Threatening GI Cancer (May 31, 2002)
2. Novartis Ophthalmics and QLT announce positive recommendation for
Visudyne(R) approval in Europe from European Committee for Proprietary
Medicinal Products (May 31, 2002)
3. Data demonstrating Zometa(R)as effective treatment for debilitating
bone complications in prostate cancer patients presented at major
urology meeting (May 27, 2002)
4. Geneva announces US District Court invalidates Augmentin(R)patents
(May 23, 2002)
Page 1 of 54 Total Pages
5. Data presented at APA meeting suggest Ritalin(R)LA (methylphenidate
hydrochloride) extended-release capsules are an effective once-daily
treatment for ADHD (May 22, 2002)
6. Two studies show Focalin(TM)(dexmethylphenidate HCl) is an effective
treatment for ADHD (May 22, 2002)
7. Data demonstrating Zometa(R) as important advance in treating lung
cancer-related bone complications presented at major oncology meeting
(May 22, 2002)
8. Aromatase inhibitors in breast cancer assessed by ASCO Committee
(May 21, 2002)
9. New head-to-head data show Glivec(R)is nearly three times more
effective as first-line treatment for chronic myeloid leukemia patients
than interferon combination therapy (May 21, 2002)
10. Glivec(R) maintains responses in patients with life-threatening
gastrointestinal tumors after one year of treatment (May 21, 2002)
11. Head-to-head worldwide study of the two leading aromatase inhibitors
shows more women respond to Femara(R) than Arimidex(R) in advanced
breast cancer (May 21, 2002)
12. Novartis launches TARGET, largest world-wide arthritis clinical trial
(May 21, 2002)
13. Gastrointestinal safety studies highlight benefits of investigational
COX-2 inhibitor (May 21, 2002)
14. Elidel(R)cream offers new non-steroid approach to treating atopic eczema
in babies and sensitive skin areas (May 16, 2002)
15. LOGIC, new 9,000-patient study, demonstrates patients switched to Lotrel
(R) from Norvasc(R) experience better blood pressure control with less
edema (May 14, 2002)
16. Starlix(R) enhances glucose control in people with impaired glucose
tolerance (May 8, 2002)
17. Glivec(R)(imatinib)* may be effective in rare blood disease according to
new report in The Lancet (May 3, 2002)
18. Interim data from MO2ART study using Neoral(R) C2 monitoring
demonstrates impressive, low rates of kidney rejection (May 2, 2002)
19. Novartis broadens horizons in post-transplant immunosuppression:
FTY720 plus Certican(TM) shows efficacy and safety in a calcineurin
inhibitor (CNI) - free regimen (May 2, 2002)
Page 2 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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)(imatinib)* Approved in European Union for Treatment
of Life-Threatening GI Cancer
Glivec is approved to treat gastrointestinal stromal tumours (GISTs), the second
indication in a record seven months
Basel, Switzerland, 31 May 2002 - Novartis announced today that, in record time,
the European Commission (EC) has issued approval for the breakthrough drug
Glivec(R) (imatinib)* for the treatment of patients with Kit (CD 117)-positive
unresectable (inoperable) and/or metastatic malignant gastrointestinal stromal
tumours (GISTs). The approval follows a positive recommendation by the EU's
Committee for Proprietary Medicine (CPMP) in February 2002. It is the second EC
approval for Glivec in seven months: the first, on 7 November 2001, was as an
oral therapy for the treatment of adult patients with Philadelphia (Bcr-Abl)
chromosome-positive chronic myeloid leukemia (CML) in chronic phase after
failure of interferon-alpha therapy, or in accelerated phase or blast crisis.
"Patients with GISTs have traditionally had very limited treatment options, so
we are especially pleased that authorities are recognising the value of Glivec
in treating this life-threatening cancer," said Daniel Vasella, MD, Chairman and
CEO of Novartis. "Glivec has already had a significant impact on the lives of
people with CML and GISTs, and we are continuing to study it in other cancers to
determine if it has the potential to help patients, either alone or in
combination with other therapies."
GISTs are the most common malignant form of sarcoma that arise in the
gastrointestinal tract. Worldwide, there are approximately 12,000 new cases each
year. The incidence is highest in people 30-60 years of age. Historically, GISTs
have been very difficult to treat due to their resistance to treatment with
available chemotherapy and radiation therapy.
For patients with metastatic or unresectable disease, GISTs were an incurable
malignancy with a median survival of 20 months and, with local recurrence, a
median survival of 9-12 months. Until now, surgery has been the only treatment
option, resulting essentially in palliation of the disease.
--------
*In the US: Gleevec(TM)(imatinib mesylate); outside the US: Glivec(R)(imatinib)
Page 3 of 54 Total Pages
About Glivec and GISTs
The EC approval for the GIST indication is supported by data from an open-label,
multinational study conducted in 147 patients with Kit (CD117) positive
unresectable and/or metastatic malignant GISTs. Patients were randomised to
receive either 400 mg or 600 mg of Glivec daily until remission. The overall
response rate was 40%, based on confirmed partial responses and stable disease
at the time of the data cut-off for the submission.
Data which have emerged since the submission for approval were presented in May
2002 at the 38th annual meeting of the American Society of Clinical Oncology
(ASCO) in Orlando, Florida, USA. The data showed that in this study, more than
60% of patients with GIST achieved confirmed partial response to Glivec, and an
additional 20% attained some degree of tumour shrinkage or stablisation of their
disease. The data also revealed that at a median follow-up of 15 months, 73% of
patients remained on the study.
Glivec, a signal transduction inhibitor, is one of the first cancer drugs to be
developed using rational drug design, based on an understanding of how some
cancer cells are generated and exhibit unrestrained growth. Glivec targets the
activity of specific enzymes called tyrosine kinases that play an important role
within certain cancer cells. The activity of a tyrosine kinase known as Kit, a
receptor that is the product of a gene called c-kit, is very often mutated and
is known to drive the growth and division of most GISTs.
Glivec To Date
The U.S. Food and Drug Administration (FDA) was the first to approve Glivec for
the GIST indication, for which it was designated as an Orphan Drug, on 1
February 2002. Glivec also is approved for the GIST indication in Switzerland,
where it was approved on 15 April 2002. To date, Novartis has received marketing
clearance for Glivec for the CML indication worldwide.
Contraindications and Adverse Events
Although the majority of patients had adverse events reported at least once
during this trial, most events were mild to moderate in severity and included
nausea, diarrhoea, periorbital oedema, muscle cramps, fatigue, headache and skin
rash. About 23% of the patients had severe drug-related side effects that
included low white blood cell counts, tumor haemorrhage and abdominal pain. In
the GIST trial submitted for registration, drug was discontinued for adverse
events in 13 patients (9% of patients). In this clinical trial, the most common
adverse events were oedema, nausea, diarrhoea, 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 contraindicated in patients
with known hypersensitivity to imatinib or any of its excipients. Women of
childbearing potential should be advised to avoid becoming pregnant while taking
Glivec.
In most countries where Glivec is approved, it is indicated for the treatment of
patients with Philadelphia chromosome-positive CML in blast crisis, accelerated
phase, or in chronic phase after failure of interferon-alpha therapy.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "shown the potential to help," "until now," "authorities
are recognizing the value," 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
Page 4 of 54 Total Pages
guaranteed and management's expectations regarding further commercialisation of
Glivec could be affected by, among other 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 materialise,
or should underlying assumptions prove incorrect, actual results may vary
materially from those anticipated, believed, estimated or expected.
About Novartis
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.
# # #
Additional information can be found at www.novartisoncologyvpo.com and at
www.novartisoncology.com.
Page 5 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 Ophthalmics and QLT announce positive recommendation for Visudyne(R)
approval in Europe from European Committee for Proprietary Medicinal Products
This represents a major step in the marketing approval process in Europe for
expanded use in patients with occult CNV secondary to age-related macular
degeneration
Basel, 31 May 2002 - Novartis Ophthalmics, the eye health unit of Novartis AG,
and QLT Inc. today announced that the Committee for Proprietary Medicinal
Products (CPMP) of the European Medicines Evaluation Agency (EMEA), has adopted
a positive opinion on Visudyne(R) (verteporfin) therapy to also include the
treatment of patients with evidence of recent or ongoing disease progression in
occult subfoveal choroidal neovascularization (CNV) secondary to age-related
macular degeneration (AMD), a leading cause of blindness among people over the
age of 50. The CPMP opinion will now be considered by the European Commission,
which should make a final decision within three months regarding marketing
authorization in the European Union.
Visudyne therapy is the only drug approved for the treatment of certain forms of
wet 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 90% of severe vision loss. Approximately 500,000
new cases of the wet form of AMD occur each year worldwide, and this estimate is
expected to grow dramatically as the population ages.
"We look forward to the European Commission's final decision and to being able
to provide Visudyne to the many patients for whom there is no approved drug
treatment currently available," said Paul Hastings, president and CEO of QLT.
This application was based on favorable two-year results from the Verteporfin in
Photodynamic Study trial (VIP), a phase IIIb clinical trial, which included 258
patients with subfoveal occult without classic CNV, who had recent disease
progression. The study showed that patients who received Visudyne therapy for 24
months had a significantly reduced risk of moderate and severe vision loss
compared to the placebo group. The results were published in the May 2001 issue
of the peer-reviewed American Journal of Ophthalmology.
"We are very pleased with the committee's recommendation for approval of
Visudyne for occult wet AMD, " said Luzi von Bidder, head of Novartis
Ophthalmics. "This positive recommendation is a very important milestone as
occult CNV represents a considerable portion of the total wet
Page 6 of 54 Total Pages
AMD population and if approved this indication could expand the current market
for Visudyne to two-thirds of the total patient population in Europe."
About AMD
AMD is caused by a growth of abnormal blood vessels (CNV) under the central part
of the retina or macula and occurs in two forms, dry and wet AMD. In the wet
form, 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 two months to three years. "Occult" and "classic" are
terms used to describe the different patterns of CNV leakage as seen on
fluorescein angiography.
About Visudyne
Visudyne therapy, the only drug approved for the treatment of some forms of wet
AMD, has treated approximately 150,000 patients worldwide. Visudyne is
commercially available in 62 countries for the treatment of predominantly
classic subfoveal CNV caused by AMD. It is also approved in 40 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
relatively painless 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 and does not affect normal/healthy blood
vessels.
Visudyne is generally well tolerated and has an excellent safety profile.
Potential side effects include injection site reactions, headaches, back pain,
blurring, decreased sharpness and gaps in vision, and in 1-5% of patients a
substantial decrease in vision with partial recovery in some patients. People
should avoid direct sunlight for five days to avoid sunburn. People with
porphyria should not be treated. For more information, visit www.visudyne.com.
Visudyne(R) is a trademark of Novartis AG.
The foregoing press release contains forward-looking statements, that can be
identified by terminology such as "should make" or "could expand", or by
discussions regarding potential new indications for existing products. 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. There are no guarantees that any of the
potential potential new indications will be commercialized in any market. Any
such commercialization can be affected by, among other things, the risk that the
CPMP opinion may be rejected by the European Commission, uncertainty regarding
the market size of the occult wet AMD population in Europe and the effect of the
CPMP opinion and pending decision of the European Commission on Visudyne sales,
other risks associated with the development and commercialization of the
treatment, including uncertainties relating to manufacturing, clinical trials,
registration, ppricing and reimbursement; patient and physician demand for the
treatment; competition; any uncertainty regarding patents and proprietary
rights; and additional 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, and Novartis AG's Form 20-F, and other filings with the US Securities
and Exchange Commission and Canadian Securities Regulatory authorities.
Page 7 of 54 Total Pages
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 global biopharmaceutical company dedicated
to the discovery, development, and commercialization of innovative therapies to
treat cancer, eye diseases and immune disorders. Combining expertise in
ophthalmology, oncology and photodynamic therapy, QLT has commercialized two
products to date, including Visudyne therapy which is the largest selling
ophthalmology product ever launched. For more information, visit our web site at
www.qltinc.com .
# # #
Page 8 of 54 Total 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
Data demonstrating Zometa(R) as effective treatment for debilitating bone
complications in prostate cancer patients presented at major urology meeting
Basel, Switzerland, 27 May 2002 - The Novartis drug Zometa(R) (zoledronic acid)
is effective for the treatment of potentially debilitating skeletal related
events from bone metastases in prostate cancer patients according to the data
presented at the 97th annual meeting of the American Urological Association
(AUA) in Orlando, Florida, USA. Patients with advanced prostate cancer are at
high risk for developing bone complications-or skeletal related events
(SREs)-which include bone pain, pathologic fractures, need for radiation or
surgery to bone, spinal cord compression and hypercalcaemia. This study marks
the first time a bisphosphonate has demonstrated efficacy in treating bone
metastases in this patient population. Further, Zometa offers patients, nurses
and clinicians a convenient 4 mg (in 100 ml of solution), 15-minute infusion
time.
"Bone metastases can result in debilitating pain, fractures and compression of
the spine and are a significant problem for patients with advanced prostate
cancer. Until now, there were few effective therapies available for these
patients," said Fred Saad, MD, Associate Professor of Urology and Director of
Urologic Oncology at the Montreal Cancer Institute, University of Montreal.
"Zometa represents a significant advance in the overall treatment of advanced
prostate cancer patients and should be a welcome addition for urologists and
oncologists in the care of their patients."
Study Design
The study was designed to investigate the efficacy of Zometa in patients with
bone complications resulting from prostate cancer, particularly with respect to
reducing the proportion of patients with SREs and delaying the time to first
SRE. A total of 643 patients with at least one bone metastasis participated in
the multicentre, randomized, placebo-controlled trial. The final analysis was
based on evaluating Zometa 4 mg (in 100 ml of solution) compared to placebo at
an infusion rate of 15 minutes, given every three weeks for 15 months.
Initially, a third arm of the study evaluated an 8 mg dose of Zometa; however,
that dose offered no efficacy advantage compared to the recommended dose (4
mg/15 minute infusion), but was associated with a higher incidence of adverse
events, including increased serum creatinine levels. Therefore, dosing on this
arm was changed to 4 mg and was not included in this efficacy analysis.
Clinical Data
The data demonstrated that 25% fewer patients taking Zometa 4 mg experienced any
SRE compared to those patients taking placebo (Zometa 33% vs. placebo 44%,
p=0.021). The 15-month data also demonstrated that fewer patients taking Zometa
4 mg had a pathologic fracture compared to those patients taking placebo (Zometa
13% versus placebo 22%, p=0.015). Patients taking Zometa 4 mg also showed a
slower rate of progression of pain compared with placebo. All
Page 9 of 54 Total Pages
patients experienced a mean increase from baseline in composite Brief Pain
Inventory (BPI) pain scores over time; however, the increases were lower at
every time point for patients treated with Zometa 4 mg compared with placebo
(statistically significant at months three and nine).
About Prostate Cancer and Bone Metastases
Bone metastases are the spread of cancerous cells from the original tumor to
bones. Bone metastases/lesions are common in prostate cancer and research
indicates bone metastases occur in 65-75% of all advanced prostate cancer
patients and often bone is the only site of metastases. Some studies have shown
that complications of metastases are the primary cause of death among patients
with prostate cancer; therefore, treating the bone metastases may successfully
improve clinical outcome. Prior to Zometa, current therapeutic options for
complications of bone metastases included hormonal therapy, surgery,
radiotherapy, chemotherapy and analgesics for pain management.
About Zometa
Zometa received U.S. FDA approval on 22 February 2002 for the treatment of
patients with multiple myeloma and patients with documented bone metastases from
solid tumors, in conjunction with standard antineoplastic therapy. These solid
tumors studied include prostate cancer, breast cancer and other solid tumor
types including renal, colorectal and lung. In prostate cancer, patients should
have progressed after treatment with at least one hormonal therapy. Zometa also
received a positive opinion for this indication from the Committee for
Proprietary Medicinal Products (CPMP) in the European Union (EU). The EU
Commission usually grants approval of products four months after a CPMP positive
opinion.
Contraindications and Adverse Events
In clinical trials in patients with bone metastases, Zometa was generally well
tolerated, with a safety profile similar to other intravenous 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. 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 bisphosphonates have been associated with reports of renal
insufficiency. Patients should have serum creatinine assessed prior to receiving
each dose of Zometa. Caution is advised when Zometa is administered with other
potentially nephrotoxic drugs. Due to the risk of clinically significant
deterioration in renal function, single doses of Zometa should not exceed 4 mg
and the duration of infusion should be no less than 15 minutes.
This release may contain forward-looking statements regarding the potential
launch of Zometa in markets in which it currently is not approved, or regarding
potential new indications for Zometa in existing markets. 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 Zometa or any potential new indications for Zometa 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 materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from those
described herein as anticipated, believed, estimated or expected.
Page 10 of 54 Total Pages
About Novartis
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.
# # #
Further information can be found at www.novartisoncologyvpo.com or at
www.novartisoncology.com.
Page 11 of 54 Total Pages
[Geneva Pharmaceuticals Logo]
Geneva Pharmaceuticals, Inc.
101 Morgan Lane, 2nd floor
Plainsboro, Nj 08536
Tel +1 609.750.4700
Internet Address:
http://www.genevarx.com
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
Geneva announces US District Court invalidates Augmentin(R)patents
Plainsboro, New Jersey, 23 May 2002 - Geneva Pharmaceuticals, Inc. ("Geneva")
announced today that the US District Court for the Eastern District of Virginia
rendered a decision in Geneva Pharmaceuticals, Inc., et al. v. GlaxoSmithKline
PLC, et al. (Civ. Act. Nos. 2:01-CV-391; 2:01-CV-677; and 2:01-CV-925)
invalidating the three remaining patents claiming GlaxoSmithKline PLC's
("Glaxo's") antibiotic Augmentin(R)(amoxycillin/clavulanate potassium).
The Court ruled that US Patent Nos. 4,525,352; 4,529,720; and 4,560,552, which
are otherwise due to expire on June 25, July 16 and December 24, 2002,
respectively, are invalid for double-patenting. The Court had previously granted
motions for summary judgment invalidating a number of other patents claiming
Augmentin which were due to expire in 2017 and 2018. Geneva has received final
approval from the US Food and Drug Administration for its generic version of
Augmentin, in several strengths and dosage forms.
Geneva Pharmaceuticals, Inc. is one of the largest prescription generic drug
companies in the US Geneva produces more than 200 products each year, with an
annual manufacturing capability exceeding 10 billion tablets and capsules.
Geneva products range across many therapeutic drug categories including
anti-infectives, anti-arthritics, cardiovasculars, gastrointestinal agents and
psychotherapeutics. Geneva is an affiliate of the 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 more information about Geneva, please see our website at
www.genevarx.com. For more information on Novartis, www.pharma.us.novartis.com
or www.novartis.com.
The foregoing press release contains forward-looking statements that can be
identified by terminology such as "will evaluate," "will examine," "will
assess," "will be assessed" 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 clinical trials will result in the
commercialization of any product in any
Page 12 of 54 Total Pages
market. Any such commercialization can be affected by, amongst other things,
uncertainties relating to product development, including the results of 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'
Form 20-F filed with the 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.
CONTACTS:
Jeremiah J. McIntyre
Geneva Pharmaceuticals, Inc.
303.438.4154
jeremiah.mcintyre@gx.novartis.com
Sandra MacTavish
Geneva Pharmaceuticals, Inc.
609.750.4704
sandra.mactavish@gx.novartis.com
Page 13 of 54 Total Pages
Novartis Pharmaceutical
Corporation
[NOVARTIS LOGO] One Health Plaza
East Hanover, Nj 07936-1080
USA
Tel +1 973 781 8300
Internet Address:
http://www.pharma.us.novartis.com
MEDIA RELEASE o COMMUNIQUE AUX MEDIAS o MEDIENMITTEILUNG
Data presented at APA meeting suggest Ritalin(R) LA (methylphenidate
hydrochloride) extended-release capsules are an effective once-daily treatment
for ADHD
Philadelphia, PA, 22 May 2002 - Data presented at the 155th Annual Meeting of
the American Psychiatric Association (APA), suggest that Ritalin(R) LA
(methylphenidate HCl) extended-release capsules, are an effective and
well-tolerated, once-daily formulation of Ritalin(R) (methylphenidate HCl),
designed to last the school day and eliminate the need for the midday dose of
Ritalin. Results from a double-blind, randomized, placebo-controlled study found
that a once-daily morning dose of Ritalin LA was effective in reducing
Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in both home and school
settings. Ritalin LA uses SODASTM technology*, a proprietary drug delivery
technology of Elan Corporation, plc.
"The data presented suggest Ritalin LA is an effective and safe once-daily
formulation of Ritalin," said Joseph Biederman, MD, Chief, Joint Program in
Pediatric Psychopharmacology, Massachusetts General Hospital, Professor of
Psychiatry, Harvard Medical School, and lead author of the study. "This
formulation would have the significant benefit of eliminating the need to take
medication during school hours."
One hundred and sixty ADHD patients, aged 6 - 12, were enrolled in a
multi-center study to compare the safety and efficacy of Ritalin LA to placebo.
After an initial single-blind screening and titration period, the patients were
randomized to receive either a once-daily, morning dose of Ritalin LA or
placebo. Efficacy was evaluated by examining the presence of ADHD symptoms in
the school and home environment. In this analysis, the primary outcome was
measured by the change from baseline in the Conners ADHD/DSM-IV total subscale
for teachers (CADS-T), a validated tool for the assessment of ADHD symptoms by
teachers. Ritalin LA was found to be clinically and statistically superior to
placebo in managing ADHD symptoms in all primary and secondary efficacy
variables.
Ritalin LA was also shown to be safe and well tolerated. The incidence of
adverse events was similar for Ritalin LA and placebo (24.6% vs. 23.9%). In this
study, Ritalin LA exhibited a low rate of discontinuation due to adverse events
versus placebo, (1.5% vs. 0.0%).
Ritalin LA is designed to deliver an immediate release of Ritalin and a second
equal release of approximately 4 hours after administration, mimicking the
pharmacokinetic profile of twice-daily Ritalin. The bimodal release formulation
of Ritalin LA provides two peak concentrations of medication, mimicking
twice-daily Ritalin but with less fluctuation. Ritalin LA provides the same
rapid onset as Ritalin and its efficacy lasts throughout the school day. Ritalin
LA may be swallowed whole with capsules, or, for children who have difficulty
swallowing, it may be administered by sprinkling the beaded contents on
applesauce.
Page 14 of 54 Total Pages
Ritalin LA was developed by Elan's drug delivery division and will be supplied
to Novartis under an exclusive worldwide royalty and manufacturing agreement
between the companies. Novartis Pharmaceuticals Corporation has
commercialization rights to Ritalin LA in the U.S.
ADHD is the most studied childhood psychiatric disorder and is supported by a
substantial body of scientific evidence. Its symptoms have been described in the
medical literature since 1902. Scientific research indicates that ADHD may be
related to disturbances in certain neurotransmitters in the brain. Novartis
supports only the proper diagnosis and treatment of ADHD.
The Novartis ADHD product portfolio includes Ritalin, Ritalin SR, and
Focalin(TM) (dexmethylphenidate), a refined formulation of Ritalin. Celgene
Corporation (Nasdaq: CELG) of Warren, New Jersey granted Novartis Pharma AG an
exclusive worldwide (excluding Canada) license covering its intellectual
property rights associated with Ritalin LA as well as Focalin. Pursuant to an
agreement between Novartis Pharma AG and Novartis Pharmaceuticals Corporation,
Novartis Pharmaceuticals Corporation markets Focalin in the U.S.
In addition, Ritalin LA, a once-daily form of Ritalin, is currently under review
at the Food and Drug Administration (FDA). Novartis Pharmaceuticals Corporation
received an approvable letter from the FDA for Ritalin LA in October 2001.
The foregoing press release contains forward-looking statements that can be
identified by forward-looking terminology such as "suggest", "is designed to",
"will be" 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. In particular,
management's expectation regarding the commercialization of Ritalin LA could be
affected by amongst other things, results of future 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 the Company's Form 20-F
filed with the 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
anticipated, believed, estimated or expected.
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and
markets leading innovative prescription drugs used to treat a number of diseases
and conditions, including central nervous system disorders, organ
transplantation, cardiovascular diseases, dermatological diseases, respiratory
disorders, cancer and arthritis. The company's mission is to improve people's
lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an
affiliate of Novartis AG (NYSE: NVS), 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.
# # #
*SODAS Technology is a trademark of Elan Corporation, plc.
Page 15 of 54 Total 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
Two studies show Focalin(TM) (dexmethylphenidate HCl) is an
effective treatment for ADHD
Philadelphia, PA, 22 May 2002 - Data from two double-blind, randomized,
placebo-controlled studies presented today at the 155th Annual Meeting of the
American Psychiatric Association (APA) demonstrate that Focalin(TM)
(dexmethylphenidate HCl) is effective in the management of the symptoms of
Attention-Deficit/Hyperactivity Disorder (ADHD) at half the dose of Ritalin(R)
(d,l methylphenidate HCl). Focalin, a refined formulation of Ritalin, contains
only the effective, or d-isomer of d,l methylphenidate HCl.
The first study consisted of 132 ADHD patients, 6 - 17 years of age, randomized
to receive Focalin, d,l methylphenidate (Ritalin), or placebo. In this study,
the primary rating scale to assess efficacy was the teacher SNAP-ADHD (Swanson,
Nolan, and Pelham) rating scale, a standard behavioral assessment tool used in
clinical trials. Secondary efficacy measures included change from baseline on
the parent-completed SNAP-ADHD Rating Scale (Parent SNAP), Clinical Global
Impression-Improvement (CGI-I) scale score, and Math Test performance.
Results of the study showed the treatment effects of Focalin can be obtained at
half the milligram dose of d,l methylphenidate. Both Focalin and d,l
methylphenidate demonstrated a substantial reduction of ADHD symptoms on primary
and secondary efficacy measures across multiple settings including teachers,
parents, clinicians and patients. In addition, Focalin, but not d,l
methylphenidate showed significant improvements in Parent SNAP (P=.0085) and
Math Test (P=.0169) scores at 6 hours post dosing compared with placebo.
The second study was conducted with 89 patients (6 - 17 years of age, all
meeting criteria for ADHD) and consisted of three phases: a 6-week, open-label
dose-titration (Part A), in which all children received Focalin in doses of 2.5
mg to 10 mg twice daily; a double-blind, placebo-controlled, 2-week withdrawal
(Part B), in which half the children previously responding to Focalin received
placebo, while half remained on Focalin; and a 44-week open-label extension
(Part C) to assess long-term efficacy and safety.
Results from the study showed that patients treated with Focalin demonstrated a
substantial reduction of ADHD symptoms on primary and secondary efficacy
measures across multiple settings, followed by a significant worsening of
symptoms upon withdrawal of the treatment as compared to placebo. The primary
efficacy variable was the percentage of Treatment Failures as assessed by the
CGI-I scale at the end of the withdrawal phase (Part B). Secondary efficacy
variables were included the Teacher SNAP-ADHD), the SNAP-ADHD rated by parents
(Parent SNAP-ADHD) at 3 PM and 6 PM, and a Math Test administered at the
clinic/office and at home.
Page 16 of 54 Total Pages
Data reported a duration of action of up to 6 hours for Focalin after the second
dose, as supported by significant improvements in both the 6-hour post dose (6
PM) Parent SNAP-ADHD scores.
"The results presented today signify that dexmethylphenidate HCl, which contains
only the active d-isomer, is a safe and effective treatment for ADHD at half the
dose of Ritalin," said Keith Conners, Ph.D., Professor Emeritus of Psychiatry
and Behavioral Sciences, Duke University Medical Center and lead author of the
study.
Both studies demonstrated that Focalin was safe and well tolerated with no
serious adverse events reported. In addition, no patients needed to discontinue
therapy due to adverse events or intolerability in the double blind phase in
each of the studies.
Focalin received marketing clearance from the Food and Drug Administration (FDA)
in November 2001 for the treatment of ADHD. Focalin is administered twice daily,
at least four hours apart. Overall, there was a low incidence of adverse events
with the majority being of mild severity. In double-blind, placebo-controlled
trials there were no discontinuations due to adverse events. In long-term
extension studies, only 7 %, or 50 of 684, of children and adults treated with
Focalin experienced an adverse event that resulted in discontinuation. Like most
drugs approved for the treatment of ADHD, and like Ritalin, Focalin is
contraindicated in patients known to be hypersensitive to the drug or to
Ritalin, in patients with glaucoma, and in patients with motor tics or with a
family history or diagnosis of Tourette's syndrome. It is also contraindicated
during treatment with monoamine oxidase inhibitors and also within a minimum of
14 days following discontinuation of a monoamine oxidase inhibitor (hypertensive
crises may result). In addition, like most drugs approved for the treatment of
ADHD, Focalin is a schedule II drug.
ADHD is the most studied childhood psychiatric disorder and is supported by a
substantial body of scientific evidence. Its symptoms have been described in the
medical literature since 1902. Scientific research indicates that ADHD may be
related to disturbances in certain neurotransmitters in the brain. Novartis
supports only the proper diagnosis and treatment of ADHD.
The Novartis ADHD product portfolio includes Ritalin, Ritalin SR, and
Focalin(TM), a refined formulation of Ritalin. Celgene Corporation (Nasdaq:
CELG) of Warren, New Jersey granted Novartis Pharma AG an exclusive worldwide
(excluding Canada) license covering its intellectual property rights associated
with Focalin as well as Ritalin LA, a once-daily form of Ritalin that is
currently under review at the FDA. Pursuant to an agreement between Novartis
Pharma AG and Novartis Pharmaceuticals Corporation, Novartis Pharmaceuticals
Corporation markets Focalin in the U.S.
In addition, Novartis Pharmaceuticals Corporation received an approvable letter
from the FDA for Ritalin LA in October 2001. Ritalin LA was developed by Elan
Corporation, plc's drug delivery division and will be supplied to Novartis under
an exclusive worldwide royalty and manufacturing agreement between the
companies. Novartis Pharmaceuticals Corporation has commercialization rights for
Ritalin LA in the U.S.
The foregoing press release contains forward-looking statements that can be
identified by forward looking terminology such as, "show", "demonstrate" "will
be" or similar expressions. Such 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. In particular, management's expectation
regarding the
Page 17 of 54 Total Pages
commercialization of Ritalin LA could be affected by amongst other things,
results from future clinical trials, 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 20F filed with the 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 anticipated, believed, estimated or expected.
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and
markets leading innovative prescription drugs used to treat a number of diseases
and conditions, including central nervous system disorders, organ
transplantation, cardiovascular diseases, dermatological diseases, respiratory
disorders, cancer and arthritis. The company's mission is to improve people's
lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an
affiliate of Novartis AG (NYSE: NVS), 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.
Celgene Corporation, headquartered in Warren, New Jersey, is an independent
biopharmaceutical company engaged primarily in the discovery, development and
commercialization of orally administered small molecule drugs for the treatment
of cancer and inflammatory diseases through gene regulation. Please feel free to
visit the Company's Web site at http://www.celgene.com.
# # #
Page 18 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
Data demonstrating Zometa(R) as important advance in treating lung
cancer-related bone complications presented at major oncology meeting
Onset of debilitating bone complications delayed for patients; Zometa is first
bisphosphonate demonstrating efficacy across a broad range of solid tumors; Data
presented at American Society of Clinical Oncology
Basel, 22 May 2002 - Study results demonstrating that Zometa(R) (zoledronic
acid) delays the initial onset of bone complications by more than two months in
patients with non-small cell lung cancer and other solid tumors were presented
at the 38th annual meeting of the American Society of Clinical Oncology (ASCO)
in Orlando, Florida, USA. Bone complications - or skeletal related events (SREs)
- represent a significant problem for cancer patients in advanced stages of
disease; they include bone pain, pathologic fractures, need for radiation or
surgery to bone, spinal cord compression and hypercalcaemia. For this patient
population Zometa represents the first and only bisphosphonate proven effective
in delaying the onset of SREs. Further, Zometa at 4 mg offers patients, nurses
and clinicians a more convenient 15-minute infusion time.
Zometa received U.S. FDA approval on 22 February 2002 for the treatment of
patients with multiple myeloma and patients with documented bone metastases from
solid tumors, in conjunction with standard antineoplastic therapy. These solid
tumors include prostate cancer, lung cancer, breast cancer and other solid tumor
types studied in the clinical trials including renal, bladder and colorectal
cancer. Zometa also received a positive opinion for this indication from the
Committee for Proprietary Medicinal Products (CPMP) in the European Union (EU).
The EU Commission usually grants approval of products four months after a CPMP
positive opinion.
"Zometa offers a tremendous benefit for cancer patients," said Lee S. Rosen, MD,
Assistant Professor of Medicine, UCLA Jonsson Comprehensive Cancer Center and
lead study investigator. "Since bone complications can be devastating, delaying
the time when a patient experiences them - by even two months - is a significant
advance."
Study Design
The study was designed to investigate the efficacy of Zometa in the prevention
of SREs across a broad range of solid tumors, other than breast cancer or
prostate cancer. A total of 773 patients were randomised to the study; 52% of
the patients had lung cancer (primarily non-small cell lung cancer) and the
remainder had other solid tumors (renal, colorectal and bladder). The final
analysis
Page 19 of 54 Total Pages
was based on evaluating Zometa 4 mg compared to placebo at an infusion rate of
15 minutes, given every three weeks for nine months. Measurements of SREs were
the endpoints and included delay in onset of SREs, proportion of patients
experiencing any SRE, and the reduction in risk of individual patients
experiencing multiple SREs (thus contributing more significantly to morbidity).
Clinical Data
In regards to multiple SREs, the data in patients with bone metastases from lung
cancer and other solid tumors demonstrate that there was a 26% reduction in the
rate at which patients experienced skeletal-related events, including multiple
SREs (p=0.006). Overall, findings demonstrate that patients receiving Zometa 4
mg at an infusion rate of 15 minutes experienced a significant delay in the
onset of SREs (230 days for Zometa vs. 155 days for placebo [p=0.007]). As the
median survival of patients with advanced cancers may be approximately six
months, a delay of more than two months provides a significant clinical benefit
to physicians and patients. Also, after nine months, patients on Zometa
experienced fewer SREs overall (38% of patients receiving Zometa vs. 47%
receiving placebo [p=0.039]).
About Zometa
Zometa is a new generation intravenous (IV) bisphosphonate. The approval for
Zometa was based on data from three large international clinical trials
evaluating more than 3,000 patients with prostate cancer, lung cancer and other
solid tumors (renal, bladder and colorectal), breast cancer and multiple
myeloma. This is the largest set of clinical trials ever conducted to evaluate
the efficacy and tolerability of a bisphosphonate in treating the complications
associated with cancerous bone lesions.
Novartis initially received marketing clearance for Zometa in the treatment of
hypercalcaemia of malignancy (HCM), also known as tumor-induced hypercalcaemia
(TIH). It has obtained approval for HCM in countries throughout the world.
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. 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 bisphosphonates have been associated with reports of renal
insufficiency. Patients should have serum creatinine assessed prior to receiving
each dose of Zometa. Caution is advised when Zometa is administered with other
potentially nephrotoxic drugs. Due to the risk of clinically significant
deterioration in renal function, which may progress to renal failure, single
doses of Zometa should not exceed 4 mg and the duration of infusion should be no
less than 15 minutes.
This release may contain forward-looking statements regarding the potential
launch of Zometa in markets in which it currently is not approved, or regarding
potential new indications for Zometa in existing markets. 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
Page 20 of 54 Total Pages
guarantees that Zometa or any potential new indications for Zometa 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 materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from those
described herein as anticipated, believed, estimated or expected.
About Novartis
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 21 of 54 Total 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
Aromatase inhibitors in breast cancer assessed by ASCO Committee
Recent studies of aromatase inhibitors - a new generation of hormone therapy -
prompt ASCO evaluation
Basel, 21 May 2002 - Data from recent studies on the use of aromatase inhibitors
in the treatment of postmenopausal women with breast cancer have generated
significant interest from the medical oncology community and have prompted
organizations to evaluate current treatment regimens. Following data presented
in December at a major breast cancer conference, the American Society of
Clinical Oncology (ASCO) convened a blue ribbon panel to review the use of
aromatase inhibitors.
Adjuvant Setting
Specific to the adjuvant breast cancer setting, the Committee reviewed the ATAC
(Arimidex [anastrozole], Tamoxifen Alone or in Combination) data and declined to
recommend the use of aromatase inhibitors at this time because of the lack of
compelling and mature data. However, Novartis is encouraged that the Committee
recognizes the importance of this category; and the Company is looking forward
to the results of its ongoing Femara(R) (letrozole) adjuvant studies that should
provide data sufficiently robust to enable the Committee to move forward with
its recommendations. Currently, the largest set of adjuvant studies evaluating
aromatase inhibitors - with more than 10,000 women participating - is evaluating
the use of Femara. One study compares Femara to placebo in women who have
remained disease free for five years of tamoxifen therapy; the other study
compares Femara to tamoxifen in various treatment sequences over a period of
five years. Results are expected in 2004.
Advanced Setting
Specific to the advanced breast cancer setting, data on aromatase inhibitors
have been presented both at this year's ASCO meeting and at the December San
Antonio Breast Cancer Symposium (SABCS 2001). At ASCO, data comparing the two
leading aromatase inhibitors Femara and Arimidex were presented and demonstrated
that 50% more women responded to Femara than Arimidex in the second-line
treatment setting. This means that Femara is more likely than is Arimidex to
shrink breast cancer tumours even in patients who had progressed after prior
anti-estrogen therapy. There were no statistically significant differences in
time to disease progression (primary endpoint) or other endpoints.
Data presented at the SABCS 2001 meeting showed that in the first-line advanced
breast cancer setting, Femara offered a statistically significant greater early
survival advantage throughout the first two years of therapy compared to
tamoxifen. In addition, approximately five years after initiation of the study
(November, 1996), more women who had begun therapy with Femara were
Page 22 of 54 Total Pages
still alive and free of tumor progression compared to those who started on
tamoxifen. No differences were seen in duration of tumor response or overall
survival.
Additional data from another study presented at the SABCS 2001 meeting
demonstrated that Femara may be more effective than tamoxifen in treating
postmenopausal women with ER and HER-2 positive breast cancer. The results are
important because HER-2 positive breast cancers in postmenopausal women are
especially difficult to treat.
Furthermore, results of the largest neo-adjuvant (pre-operative) trial
evaluating endocrine agents demonstrated that Femara is a more effective therapy
for postmenopausal women with hormone receptor positive tumours than tamoxifen.
In 324 postmenopausal women with hormone-sensitive breast cancer, the number of
clinical responses was significantly higher for Femara than for tamoxifen and
significantly more women on Femara underwent breast-conserving surgery compared
to tamoxifen.
About Femara
Femara, an aromatase inhibitor, is an oral once-a-day first-line treatment for
postmenopausal women with hormone receptor positive or hormone receptor unknown
locally advanced or metastatic breast cancer. It is also approved for the
treatment of advanced breast cancer in women with disease progression after
prior antiestrogen therapy. Femara is currently available in more than 75
countries worldwide. Not all indications are available in each country.
Femara is contraindicated in patients with known hypersensitivity to Femara or
any of its excipients. Femara is generally well tolerated and adverse reactions
rates in the first-line study in which Femara was compared to tamoxifen were
similar with those seen in second-line studies. The most commonly reported
adverse events for Femara vs. tamoxifen were bone pain (20% vs. 18%), hot
flushes (18% vs. 15%), back pain (17% vs. 17%), nausea (15% vs. 16%), dyspnea or
labored breathing (14% vs. 15%), arthralgia (14% vs. 13%), fatigue (11% vs.
11%), coughing (11% vs. 10%), constipation (9% vs. 9%), chest pain (8% vs. 8%)
and headache (8% vs. 7%). Femara may cause fetal harm when administered to
pregnant women. There is no clinical experience to date on the use of Femara in
combination with other anticancer agents. The incidence of peripheral
thromboembolic events, cardiovascular events, and cerebrovascular events was <=
2%.
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 "looking forward to," "should provide data," "may be more
effective" or similar expressions, or by discussions of potential new treatments
or indications for Femara. 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 can be no guarantee that any new
treatments or indications for Femara will be commercialized in any market. 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. Some of these are uncertainties relating to unexpected regulatory
delays; unexpected clinical trial results with Femara; additional analysis of
clinical data; new data; government regulation or competition in general; as
well as factors discussed in the Company's Form 20-F filed with the 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.
Page 23 of 54 Total Pages
About Novartis
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.
# # #
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 head-to-head data show Glivec(R) is nearly three times more effective as
first-line treatment for chronic myeloid leukemia patients than interferon
combination therapy
Data Comparing Efficacy of Glivec to Interferon/Chemotherapy Combination
Presented at American Society of Clinical Oncology Meeting
Basel, 21 May 2002 - Data from the first ever head-to-head study of the Novartis
drug Glivec(R) (imatinib)* demonstrate that Glivec is nearly three times more
effective in achieving a cytogenetic response in the first-line treatment of
newly diagnosed chronic myeloid leukemia (CML) patients than the combination of
interferon-alpha and cytarabine arabinoside, a form of chemotherapy (IFN/Ara-C).
In addition, Glivec significantly delayed the time to progression to the more
advanced stages of CML compared to IFN/Ara-C. These new data were presented at
the 2002 meeting of the American Society of Clinical Oncology (ASCO) in Orlando,
Florida, USA. Glivec is a novel therapy that offers new hope to patients
suffering from a disease that previously had very limited treatment options, and
that has provided researchers with new insights into the biological mechanisms
of cancer.
"The results clearly show that the earlier Glivec is used in treating CML, the
better the response," said lead investigator Brian Druker, MD, Professor of
Medicine, Oregon Health Sciences University. "These data are so supportive of
using Glivec in patients newly-diagnosed with CML that physicians need to
strongly reconsider the current treatment options for CML patients."
Clinical Data
The International Randomised Study of Interferon vs. STI571 (IRIS) is an
open-label Phase III trial that enrolled 1106 patients in 177 centres across 16
countries. There were two arms to the study: one arm received Glivec at 400
mg/day, the other arm received IFN at a target dose of 5 MIU/M2/day with Ara-C
20 mg/M2/day. The results presented were based on data collected up to 12 months
after the last patient was randomised; the median follow-up was 14 months. The
results showed that patients had achieved major and complete cytogenetic
responses of 84% and 69% (Ph<35%), compared with patients in the IFN/Ara-C arm,
who experienced major and complete cytogenetic responses of 30% and 11.5%. The
complete haematologic response rates were 96% for the Glivec arm and 67% for the
IFN/Ara-C arm.
Last January, based on a review of the six-month positive results for Glivec, an
Independent Data Monitoring Board (IDMB) requested a change in the study
protocol that enabled patients receiving
Page 25 of 54 Total Pages
IFN/Ara-C to switch to Glivec if they had not achieved a major cytogenetic
response after one year of the combination therapy.
At the time of this analysis, fewer than 1% of Glivec-treated patients crossed
over to the IFN/Ara-C therapy, compared with 39% of IFN/Ara-C-treated patients
who crossed over to Glivec due to insufficient efficacy or intolerance.
In the study, patients taking Glivec had an improved overall progression-free
survival compared to those taking IFN/Ara-C. The estimated rate of
progression-free survival at 12 months was 97.2% in the Glivec arm as compared
with 80.3% in the patients randomised to IFN+Ara-C (P<0.001). Progression was
defined as progression to accelerated phase or blast crisis, rapid increase in
white blood cell count; loss of either complete haematologic response or major
cytogenetic response; or death during treatment. In particular, the estimated
probability of being free of progression to accelerated phase or blast crisis at
12 months was also significantly superior in the Glivec arm (98.5%) as compared
to the control group (93.1%), regardless of crossover.
The safety profile with Glivec was similar to that of previous Phase II studies,
and was superior to that of the IFN/Ara-C combination regimen. The most frequent
adverse events with Glivec were mild to moderate superficial oedemas, muscle
cramps, skin rash and nausea. The most frequent adverse events with IFN/Ara-C
were nausea, fatigue, headache and diarrhoea. In the Glivec arm, only 2% and
0.7% of patients discontinued from the study or crossed over the control arm for
safety reasons. In contrast, in the IFN/Ara-C arm, 6% and 23% of patients
discontinued from the study or crossed over for safety reasons, respectively.
The Philadelphia chromosome (Ph) is the genetic abnormality that characterises
most cases of CML; it is the result of the transfer of DNA between chromosomes 9
and 22. Cytogenetic response, regarded as the ultimate goal of CML treatment, is
the disappearance or reduction of the number of cells containing the
Philadelphia chromosome. In CML, therefore, a "complete cytogenetic response"
indicates that there are no longer any Ph+ cells detected.
"Novartis is extremely pleased with the performance of Glivec in the IRIS
study," said David Parkinson, MD, Vice President, Clinical Research, Novartis
Oncology. "Based upon these results, we will shortly submit to health
authorities globally an application for use of Glivec as first line-treatment in
CML."
This study was one of several posters and presentations about Glivec and CML at
the ASCO meeting. Topics covered by these studies include data in newly
diagnosed Philadelphia-chromosome positive chronic phase CML patients;
preliminary data from a dosing study and cost effectiveness data.
Contraindications and Adverse Events
The majority of patients treated with Glivec experience adverse events at some
time. Most events were of mild to moderate grade and treatment was discontinued
for adverse events only in 2% of patients in chronic phase, 3% in accelerated
phase and 5% in blast crisis. The most common side effects included nausea,
fluid retention, vomiting, diarrhoea, haemorrhage, muscle cramps, skin rash,
fatigue, headache, dyspepsia and dyspnoea, as well as neutropenia and
thrombocytopenia.
In most countries where Glivec is approved, it is indicated for the treatment of
patients with Philadelphia chromosome-positive CML in blast crisis, accelerated
phase, or in chronic phase after failure of interferon-alpha therapy. The
effectiveness of Glivec is based on overall haematologic and cytogenetic
response rates.
Page 26 of 54 Total Pages
The foregoing release contains forward-looking statements that can be identified
by discussions of potential new indications for Glivec. 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 can
be no guarantees that the aforementioned clinical trials will result in the
commercialisation of any new indication for Glivec in any market. Any such
commercialisation can 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.
About Novartis
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 27 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
Glivec(R) maintains responses in patients with life-threatening gastrointestinal
tumors after one year of treatment
New data on gastrointestinal stromal tumors (GISTs) presented at American
Society of Clinical Oncology annual meeting
Basel, 21 May 2002 - New data demonstrate that more than 60% of patients with an
inoperable and life-threatening form of gastrointestinal cancer are continuing
to respond to the Novartis drug Glivec(R) (imatinib)* or maintain stable disease
after one year of treatment. The data also show that more than 80% of patients
overall experienced significant tumor shrinkage or stabilization of tumor
growth. The data were presented at the 38th annual meeting of the American
Society of Clinical Oncology (ASCO) in Orlando, Florida, USA.
"These results are quite impressive, especially when you contrast them with
current treatment alternatives, which are very limited," said Margaret von
Mehren, MD, Associate Member of the Fox Chase Cancer Centre in Philadelphia, PA,
USA, and a lead investigator on the study. "GISTs are an extremely difficult
cancer to treat, so the fact that a convenient, oral, once daily therapy, like
Glivec, can offer this type of response is very welcome news to patients and
oncologists."
GISTs are the most common malignant form of sarcoma that arises in the
gastrointestinal tract. Historically, they 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 (inoperable)
disease, GISTs represented an incurable malignancy with a median survival of
approximately 10 to 12 months. Until now, surgery has been the only effective
treatment option for most GISTs, resulting essentially in palliation of the
disease.
Clinical Data
In this randomised Phase II study, 147 patients with inoperable and/or
metastatic GISTs were treated with either 400 or 600 mg of Glivec orally per
day, and patients were monitored beginning one months after initial treatment.
With a median follow-up of 15 months, the overall rate of partial response was
>60% based on Southwest Oncology Group (SWOG) criteria. At the 15 months
follow-up, approximately 70% of the patients remained free of treatment failure
(had not progressed, discontinued treatment or died). More than 60% of patients
had tumors that shrank by at least half; 20% had tumors that shrank by
one-quarter to one-half, or stabilised. Only 12% of patients did not respond to
treatment. Results did not differ substantially between the two dosages used in
the study. To date, the median survival time has not been established.
Page 28 of 54 Total Pages
This study was one of approximately 15 posters and presentations about Glivec
and GIST at the ASCO meeting. Topics covered by these studies include the
possibility of predicting potential response to Glivec based on the presence of
specific genetic mutations, preliminary data from a large dosing study and an
overview of effective screening techniques for measuring the response of GIST to
treatment.
"Glivec continues to provide new insights into the molecular pathways driving
certain cancers, such as GIST," said David Parkinson, MD, Vice President,
Clinical Research, Novartis Oncology. "The understanding it has afforded should
allow us to identify approaches that may further enhance the patient benefit of
Glivec in GIST, as well as potentially in other cancers and conditions."
About Glivec
Glivec, a signal transduction inhibitor, is one of the first cancer drugs to be
developed using rational drug design, based on an understanding of how some
cancer cells work. Glivec targets the activity of a type of enzymes called
tyrosine kinases that play an important role within certain cancer cells.
Studies have shown the effectiveness of Glivec in treating Philadelphia
chromosome-positive chronic myeloid leukemia (CML) and in gastrointestinal
stromal tumors GIST, driven by the cancer-causing proteins Bcr-Abl and Kit
respectively. Glivec was approved by the US Food and Drug Administration (FDA)
in February 2002 for the treatment of patients with Kit (CD 117) positive
unresectable (inoperable) and/or metastatic malignant GISTs. Prior to the
availability of Glivec, patients with GIST had no effective treatment options
beyond surgery. In the EU, the Committee for Proprietary Medicinal Products
(CPMP) issued a positive opinion for the GIST indication in February 2002, and
approval is anticipated shortly.
Contraindications and Adverse Events
Although the majority of patients had adverse events reported at least once
during this trial, most events were mild to moderate in severity and included
nausea, diarrhoea, periorbital oedema, muscle cramps, fatigue, headache and skin
rash. About 23% of the patients had severe drug-related side effects that
included low white blood cell counts, tumor haemorrhage and abdominal pain. In
the GIST trial submitted for registration, drug was discontinued for adverse
events in 13 patients (9% of patients). In this clinical trial, the most common
adverse events were oedema, nausea, diarrhoea, 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 contraindicated in patients
with known hypersensitivity to imatinib or any of its excipients. Women of
childbearing potential should be advised to avoid becoming pregnant while taking
Glivec.
In most countries where Glivec is approved, it is indicated for the treatment of
patients with Philadelphia chromosome-positive CML in blast crisis, accelerated
phase, or in chronic phase after failure of interferon-alpha therapy. The
effectiveness of Glivec in CML is based on overall haematologic and cytogenetic
response rates.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "is anticipated," "should allow," "potentially" and
"further enhance," 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
Page 29 of 54 Total Pages
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 US 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.
About Novartis
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 30 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
Head-to-head worldwide study of the two leading aromatase inhibitors shows more
women respond to Femara(R) than Arimidex(R) in advanced breast cancer
Study in second-line breast cancer setting presented at American Society of
Clinical Oncology meeting shows significantly greater objective response rate
with Femara
Basel, 21 May 2002 - In a head-to-head worldwide study of the two leading
aromatase inhibitors, data demonstrate that 50% more women respond to Femara(R)
(letrozole) than to Arimidex(R) (anastrozole) in advanced breast cancer. This
means that more women treated with Femara had at least a 50% reduction in the
size of their tumour. The data from this multicentre, international study of 713
postmenopausal women with ER+ and/or PgR+ or ER/PgR status unknown receiving
second-line treatment for advanced disease were presented at the 38th annual
meeting of the American Society of Clinical Oncology (ASCO).
"It is becoming increasingly evident that aromatase inhibitors are challenging
and are likely to replace tamoxifen in the treatment of postmenopausal women
with endocrine-dependent breast cancer. Studies like this are critical because
they provide evidence to identify the aromatase inhibitor most likely to work
best," said Carsten Rose, M.D., Director, Department of Oncology,
Universitetkliniken, Onkologiska Klinik, Lund, Sweden, and lead investigator in
the study. "The data in this trial show that more women respond to Femara than
to Arimidex, which is important information for physicians to consider when
treating advanced breast cancer patients."
Study Design
The data are from a randomised, open-label study of 713 postmenopausal women who
were either oestrogen and/or progesterone receptor positive (ER+ and/or PgR+) or
ER/PgR status unknown. The study was conducted in 19 countries and compared the
efficacy of Femara vs. Arimidex in women with metastatic breast cancer following
failure of anti-oestrogen therapy (e.g., tamoxifen).
The primary and secondary endpoints of the study were time to disease
progression, objective response rate, duration of objective response, overall
clinical benefit, time to treatment failure, and survival. Patients were
randomly allocated Femara 2.5 mg once-daily or Arimidex 1 mg once-daily.
The data show that 50% more women responded to Femara than to Arimidex (based on
objective response rate) [Femara group 19% vs. Arimidex group 12%, P=0.013].
Complete response rate
Page 31 of 54 Total Pages
was 7% for Femara vs. 4% for Arimidex. No statistically significant differences
were seen in time to disease progression (primary endpoint) or other endpoints.
The data also show that overall response rate in patients with soft tissue
disease (i.e. soft tissue dominant, no bone or visceral involvement) was
two-times higher for women receiving Femara compared to women receiving Arimidex
(Femara 37% vs. Arimidex 19%). In viscera dominant disease (viscera +/- bone +/-
soft tissue) overall response rate to Femara was also higher than to Arimidex
(Femara 14% vs. Arimidex 10%). There were no statistically significant
differences in any other endpoints.
Both Femara and Arimidex were generally well-tolerated and there were no
statistically significant differences between treatment arms in reported
frequencies of adverse events, including serious adverse events.
"The use of aromatase inhibitors is increasing and physicians need compelling
data by which they can make the right choice for the treatment of breast
cancer," said David Parkinson, M.D., Vice President, Clinical Research, Novartis
Oncology. "The consistent efficacy and overall performance of Femara in the
various clinical settings is extremely encouraging, and Novartis is looking
forward to the results of the ongoing Femara adjuvant studies."
Data Demonstrates Consistent Performance of Femara
Femara Offers Enhanced Inhibition of Oestrogen and Total Body Aromatization
Compared to Arimidex.
The head-to-head results represent the most recent data in a series of studies,
which have compared the third generation aromatase inhibitors Femara and
Arimidex. In pre-clinical studies, it had been shown that in human and animal
cell systems, letrozole was consistently at least 10-fold more potent than
anastrozole in inhibiting intracellular aromatase.
These pre-clinical studies were followed by a study comparing the ability of
Femara and Arimidex to inhibit total body aromatisation and suppress plasma
oestrogen levels in 12 postmenopausal women with metastatic breast cancer.
Hormone sensitive breast cancers rely on oestrogen for growth. In this study,
Femara was shown to be a more effective inhibitor of total body aromatisation
and suppressor of plasma oestrogen levels than Arimidex (that is, two out of
three oestrogen components were more significantly suppressed by Femara). The
differences between the two drugs were statistically significant in favour of
Femara; however, the clinical relevance of this finding is yet to be determined.
The data from the head-to-head study of Femara versus Arimidex presented at ASCO
are the most recent in a series of pre-clinical and clinical studies that
demonstrate that Femara is a more effective aromatase inhibitor than Arimidex at
inhibiting aromatase and achieving a greater objective response rate.
Femara versus tamoxifen --Survival Data in First-Line Setting
These new data add to the growing body of medical and scientific knowledge
regarding Femara. Reported at the San Antonio Breast Cancer Conference in
December 2001 were the results of a study of 907 postmenopausal women comparing
Femara to tamoxifen as first-line therapy in women with locally advanced or
metastatic breast cancer. The results demonstrated that Femara had a
statistically significant survival advantage compared to tamoxifen throughout
the first two years of therapy. No other aromatase inhibitor has shown a
survival advantage vs. tamoxifen to date. The data also demonstrated that,
approximately five years after initiation of the study
Page 32 of 54 Total Pages
(November, 1996), more women who had begun their therapy on Femara were still
alive and free of tumour progression compared to those who started on tamoxifen
(minimum treatment duration in patients still on first-line treatment at the
cut-off date for analysis was three years). In addition, patients taking Femara
had a 78% greater chance of responding to treatment than patients treated with
tamoxifen, and the chance that their tumours would progress was 28% less with
Femara than with tamoxifen.
Femara Efficacy in the Neo-Adjuvant Setting
The results of the largest neo-adjuvant (pre-operative) trial evaluating
endocrine agents demonstrated that Femara is a more effective therapy for
postmenopausal women with hormone receptor positive tumours than tamoxifen. In
the Phase III, randomised, controlled trial, Femara or tamoxifen was
administered for four months prior to surgery to reduce tumour size. In 324
postmenopausal women with hormone-sensitive (ER+ and/or PgR+), large localised
or locally advanced breast cancers not amenable to breast-conserving surgery,
the number of clinical responses was significantly higher for Femara than for
tamoxifen (55% versus 36%, P<0.001). Significantly more women on Femara
underwent breast-conserving surgery compared to tamoxifen (45% versus 35%,
P=0.022).
In addition, after adjustment for tumour size, nodal involvement and age, the
odds of undergoing breast-conserving surgery were increased by more than 65% for
Femara compared with the odds for tamoxifen (P=0.0508). Both Femara and
tamoxifen were equally well-tolerated.
About Femara
Femara, an aromatase inhibitor, is an oral once-a-day first-line treatment for
postmenopausal women with hormone receptor positive or hormone receptor unknown
locally advanced or metastatic breast cancer. It is also approved for the
treatment of advanced breast cancer in postmenopausal women with disease
progression following antioestrogen therapy, and as neo-adjuvant (pre-operative)
therapy. Femara is currently available in more than 75 countries worldwide. Not
all indications are available in each country.
In postmenopausal women, the primary source of oestrogen is from fat, liver,
muscle, and breast tissue through a process that turns adrenal androgens into
oestrogen, which stimulates the growth of certain hormone-dependent cancer
cells. A breast tumour itself also may generate oestrogen. Femara works by
binding to the enzyme aromatase and blocking it from converting adrenal
androgens to oestrogen in these tissues.
Femara is contraindicated in patients with known hypersensitivity to Femara or
any of its excipients. Femara is generally well tolerated and adverse reactions
rates in the first-line study in which Femara was compared to tamoxifen were
similar with those seen in second-line studies. The most commonly reported
adverse events for Femara vs. tamoxifen were bone pain (20% vs. 18%), hot
flushes (18% vs. 15%), back pain (17% vs. 17%), nausea (15% vs. 16%), dyspnoea
or labored breathing (14% vs. 15%), arthralgia (14% vs. 13%), fatigue (11% vs.
11%), coughing (11% vs. 10%), constipation (9% vs. 9%), chest pain (8% vs. 8%)
and headache (8% vs. 7%). Femara may cause fetal harm when administered to
pregnant women. There is no clinical experience to date on the use of Femara in
combination with other anticancer agents. The incidence of peripheral
thromboembolic events, cardiovascular events, and cerebrovascular events was <=
2%.
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 "becoming
Page 33 of 54 Total Pages
increasingly," "are likely to," "most likely to" or similar expressions, or by
discussions of strategy, plans or intentions. Such forward-looking statements
involve known and unknown risks, uncertainties and other factors that may cause
actual results with Femara to be materially different from any future results,
performance or achievements expressed or implied by such statements. 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. Some of these are uncertainties relating to unexpected regulatory
delays; unexpected clinical trial results with Femara; additional analysis of
clinical data; new data; government regulation or 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 materialize, or should
underlying assumptions prove incorrect, actual results may vary materially from
those described herein as anticipated, believed, estimated or expected.
About Novartis
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 34 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 launches TARGET, largest world-wide arthritis clinical trial
Basel, 21 May 2002 - Novartis' investigational drug PrexigeTM
(lumiracoxib/COX189) is the focus of the world's largest arthritis clinical
trial, TARGET (Therapeutic Arthritis Research & Gastrointestinal Event Trial) to
date. Prexige is an innovative COX-2 inhibitor currently being studied for the
treatment of symptoms of arthritis and pain. Sponsored by Novartis, TARGET will
evaluate the safety, tolerability and efficacy of Prexige compared with the
non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen and naproxen over 12
months.
TARGET will examine, as a primary objective, the gastrointestinal safety of
Prexige compared with the NSAIDs, as well as cardiovascular safety as a
pre-specified secondary endpoint. "TARGET is the first COX-2 inhibitor
gastrointestinal safety trial where cardiovascular safety will be assessed as
one of the pre-specified endpoints," said Thomas Schnitzer, MD, Director of the
Office of Clinical Research and Training at Northwestern University and a lead
investigator for the study. The trial will evaluate the incidence of complicated
gastrointestinal ulcers and cardiovascular events in patients taking and not
taking low-dose aspirin for cardioprotection in combination with arthritis
medication.
"With the increasing use of COX-2 inhibitors, it is essential to provide data
showing that Prexige is a safe therapeutic option for the treatment of
osteoarthritis," said Joerg Reinhardt, Head of Development, Novartis Pharma AG.
"The launch of TARGET confirms Novartis' strong commitment to the development of
new treatment alternatives for the millions who suffer with arthritis and pain
and still have unmet needs."
This study will evaluate more than 18,000 patients worldwide. Participants will
be men and women aged 50 years or older who are symptomatic sufferers of
osteoarthritis. TARGET is an international, multicenter, stratified, randomized,
double-blind, double-dummy active-controlled, parallel-group trial. The TARGET
protocol has been reviewed by the US Food and Drug Administration.
Osteoarthritis, the most common form of arthritis, is characterized by the
breakdown of cartilage in joints, causing affected bones to rub against each
other. This often leads to inflammation, pain and loss of function. Globally,
osteoarthritis accounts for half of all chronic conditions in people aged 65 and
above. It is estimated that more than 25 million Europeans and more than 20
million people in the US are affected by osteoarthritis, most of them women.
Page 35 of 54 Total Pages
The economic impact of musculoskeletal diseases, including osteoarthritis, is
substantial, and costs the US nearly USD 65 billion per year in direct expenses,
lost wages and production. Risk factors associated with osteoarthritis include
accidents, age, joint injuries due to sports, obesity, or work-related activity.
The foregoing press release contains forward-looking statements that can be
identified by terminology such as "will" or similar expressions or by
discussions regarding the potential outcome of the COX189-TARGET clinical trial.
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 clinical trials will
have any particular result, or that the COX189-TARGET clinical trial will result
in the commercialization of any product in any market. Any such
commercialization can be affected by, amongst other things, uncertainties
relating to product development, including the actual outcome of the
COX189-TARGET clinical trial itself, 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 36 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
Gastrointestinal safety studies highlight benefits of investigational COX-2
inhibitor
First data on PrexigeTM demonstrate strong gastrointestinal safety profile
compared to Celecoxib, Ibuprofen and Naproxen
Basel, 21 May 2002 - Clinical results from three studies to be presented at
Digestive Disease Week showed that gastrointestinal injuries in patients taking
Prexige(TM) (lumiracoxib/COX189), an investigational COX-2 inhibitor, were
comparable to celecoxib and significantly lower than commonly-used nonsteroidal
anti-inflammatory drugs (NSAIDs). These data support the strong gastrointestinal
safety of Prexige, an innovative COX-2 inhibitor being developed by Novartis for
the treatment of symptoms of arthritis and pain.
Traditional NSAIDs, such as ibuprofen and naproxen, have been proven effective
in relieving arthritis and pain but are known to cause ulcers in the lower
stomach, or gastroduodenum in some patients.
Findings from one 13-week study of 1 042 osteoarthritis patients showed that use
of therapeutic doses of Prexige (200 mg and 400 mg once a day) resulted in a
significantly (p<0.01) lower gastroduodenal ulcer rate than ibuprofen (three
times a day at 800 mg) at an anti-inflammatory dose and a rate similar to
celecoxib (once a day at 200 mg).
A second 7-day study evaluated the gastroduodenal effects of Prexige (200 mg
twice a day) compared to naproxen (500 mg twice a day) and placebo, showing that
in 60 healthy male subjects Prexige was well tolerated and effects on the
gastroduodenum were similar to that of placebo. No erosions were detected in
participants in either the Prexige group or the placebo group. Duodenal erosions
were detected in sixty-five percent of patients taking naproxen.
Results of a third 8-day study in 25 healthy volunteers demonstrated that
Prexige once a day at 800 mg (twice the anticipated maximum dose for Prexige) is
a COX-2 inhibitor that causes little or no injury to the lining of the
gastrointestinal tract when compared to naproxen (500 mg twice a day) which
caused gastric erosions in seventy-five percent of patients.
Page 37 of 54 Total Pages
About Prexige
Prexige is an innovative COX-2 inhibitor being developed for the treatment of
symptoms of arthritis and pain.
Additional safety studies are currently underway to evaluate the safety and
efficacy of Prexige, including TARGET (Therapeutic Arthritis Research &
Gastrointestinal Event Trial). TARGET will examine, as a primary objective, the
gastrointestinal safety of Prexige compared with the NSAIDs ibuprofen and
naproxen, as well as cardiovascular safety as a pre-specified secondary
endpoint. The study will evaluate more than 18 000 patients world-wide making it
the largest arthritis clinical study undertaken to date. TARGET will compare the
safety and efficacy of Prexige to commonly used NSAIDs, ibuprofen and naproxen,
over 12 months.
The foregoing press release contains forward-looking statements that can be
identified by terminology such as "will examine", "will evaluate", "will
compare" or similar expressions, or by discussions of potential new 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 the aforementioned clinical trials will
result in the commercialisation of any product in any market. Any such
commercialisation can be affected by, amongst other things, uncertainties
relating to product development, including the results of 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 the Company's Form
20-F filed with the US 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 38 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
Elidel(R) cream offers new non-steroid approach to treating atopic eczema in
babies and sensitive skin areas
Elidel is also proven effective in treating atopic eczema in adults
Basel, 16 May 2002 - Atopic eczema affecting babies and sensitive skin areas
such as the face has been successfully treated with the new non-steroid cream
Elidel(R) (pimecrolimus), according to data presented at the Society for
Investigative Dermatology congress in Los Angeles, USA, today. Studies(1) in
patients aged 3 months to 18 years showed that on the face and neck, where
treatment with topical corticosteroids is often restricted because of potential
side effects such as skin thinning, Elidel reduced the severity of the eczema by
an average of 64% over 6 weeks. This compared with only a 12% reduction on
average for patients treated with a vehicle cream. In a long-term management
study(2), 64% of 204 infants aged 3 to 23 months with the itching, red skin
condition were managed without any topical corticosteroids over 12 months by
using moisturisers for dry skin and starting Elidel treatment at the first signs
or symptoms. This compared with only 35% of infants in the control group.
"Since their introduction 50 years ago, topical corticosteroids have been the
mainstay of treatment for atopic eczema or atopic dermatitis, as it is otherwise
called," said Professor Alexander Kapp, Chairman and Director of the Department
of Dermatology and Allergology at the Hannover Medical University, Germany.
"However, for infants and sensitive skin areas such as the face, topical
steroids are either not recommended or only the mildest should be used because
of concerns over side effects. As eczema typically begins in childhood and
commonly occurs on the face, I am sure physicians will welcome a therapy that
can be safely used on all skin surfaces."
A further study(3) in adults with moderate to severe eczema showed that itching
- considered the most bothersome symptom of eczema - was significantly relieved
after 3 days of treatment with Elidel compared with those receiving a vehicle
cream.
A prescription-only medicine, Elidel was first launched in the USA in February
this year for the treatment of mild to moderate atopic eczema in patients aged
two years and older. The manufacturers of Elidel - Novartis - plan to hold
further discussions with the Food and Drug Administration in the USA this year
regarding the use of Elidel in infants under 2 years of age.
Page 39 of 54 Total Pages
In March, 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. Elidel is expected to be available in
Denmark around mid-year. Novartis is seeking approvals in other countries in
Europe and elsewhere worldwide.
More than 4 000 patients have now been treated with Elidel in clinical trials.
The incidence of adverse events has been low, the most common reported side
effect being a mild-to-moderate temporary feeling of warmth or burning on the
skin where the cream was applied. This occurred in 8% of children aged two to 17
years and in 10% of adults.
About Elidel
Discovered by the Novartis Research Institute in Vienna, Austria, Elidel
contains the active ingredient 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 in the skin. 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 "plan", "is expected," or
similar expressions, or by discussions regarding potential new indications for
Elidel, or the potential approval of Elidel in additional markets. 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 new indications for Elidel in any market, or
that Elidel cream will be commercialized in any additional market. Any such
results 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 20-F 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 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
References: (All of the following abstracts are accepted for presentation at the
Society for Investigative Dermatology, Los Angeles, USA, 15 - 17 May 2002)
1. Pariser D et al. Efficacy and local tolerability of pimecrolimus cream
1% in the treatment of atopic dermatitis in the face/neck region of
pediatric subjects
2. Kapp A et al. Treatment with pimecrolimus cream 1% is corticosteroid
sparing in infants with atopic dermatitis
3. Meurer M et al. Pimecrolimus cream 1% provides significant and rapid
relief of pruritus and improves disease control and quality of life
in atopic dermatitis in adults
Page 40 of 54 Total Pages
Investor Relations Novartis International AG
CH-4002 Basel
Switzerland
[NOVARTIS LOGO] 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 -
LOGIC, new 9,000-patient study, demonstrates patients switched to Lotrel(R) from
Norvasc(R) experience better blood pressure control with less edema
Two other studies, ALERT and SHIELD, evaluate Lotrel efficacy in diabetic
hypertension, arterial compliance, left ventricular hypertrophy
Basel, 14 May 2002 - Novartis today announced that three new studies evaluating
the efficacy and safety of Lotrel(R) (amlodipine/benazepril HCl) in a broad
range of hypertensive patients will be presented this week during the 17th
annual meeting of the American Society of Hypertension (ASH). Lotrel is a
single-capsule combination of two antihypertensive medications: amlodipine, the
calcium channel blocker (CCB) found in Norvasc(R) and the angiotensin converting
enzyme (ACE) inhibitor Lotensin(R) (benazepril).
The studies - LOtrel: Gauging Improved Control (LOGIC), Study of HypertensIon
and the Efficacy of Lotrel in Hypertensive Diabetics (SHIELD) and A Lotrel
Evaluation of Hypertensive Patients with ARterial Stiffness and Left Ventricular
HyperTrophy (ALERT) -demonstrate Lotrel's effects in treating a broad range of
hypertensive patients, including those with diabetes or arterial stiffness and
left ventricular hypertrophy. The LOGIC study also demonstrated that Lotrel
alleviated a common side effect of Norvasc monotherapy known as pedal edema
(swelling of the feet and legs). More than 9,500 patients were involved in these
studies.
Lotrel is available in the US only, where it is one of the fastest growing
branded high blood pressure therapies on the market. Lotrel is indicated for
hypertension, but not for initial therapy, and was approved for marketing in the
U.S. in 1995.
"Physicians are embracing the value of combination therapy with an ACE inhibitor
and calcium channel blocker for tough-to-treat hypertensive patients because the
combination provides superior blood pressure control with excellent
tolerability. The new data will make physicians more confident in prescribing
Lotrel for a wide array of hypertensive patients," said William Daley, MD, MPH,
Executive Director, Cardiovascular & Metabolism, US Medical Affairs, Novartis
Pharmaceuticals Corporation. "Novartis will continue to research ACE/CCB
combination therapy. We are currently conducting studies to evaluate the
efficacy of Lotrel in African-Americans, patients with diabetes and hypertension
and in those with isolated systolic hypertension."
Page 41 of 54 Total Pages
Lotrel Studies Presented at American Society of Hypertension Meeting
LOGIC (LOtrel: Gauging Improved Control)
Patients switched from amlodipine to Lotrel in a practice-based setting
experienced better blood pressure control with less pedal edema.
LOGIC is a four-week, multi-center, practice-based, open-label study that
evaluated the antihypertensive efficacy and tolerability of once-daily Lotrel
versus amlodipine in 9,208 patients with mild-to-moderate hypertension. The
patients were divided into two groups: patients who did not achieve blood
pressure control with amlodipine (Group I) and patients whose blood pressure was
controlled, but who experienced unacceptable edema with amlodipine (Group II).
The 7,468 patients in Group I whose blood pressures were not adequately
controlled with either 5 mg or 10 mg of amlodipine (mean sitting diastolic blood
pressures (MSDBP) of =>90 mmHg but <=110 mmHg) were switched to either 5 mg/10
mg or 5 mg/20 mg of Lotrel. The decision to switch patients to Lotrel 5 mg/10 mg
or 5 mg/20 mg was based on the treating physicians' clinical judgment. An
additional 1,739 patients taking amlodipine (Group II) who had controlled blood
pressure (<=90 mmHg) but who experienced unacceptable amlodipine-induced pedal
edema were also switched to Lotrel.
After four weeks of treatment, Group I patients experienced significant
reductions in MSDBP of 11.5 mmHg and in mean sitting systolic pressure (MSSBP)
of 15.6 mmHg when they were switched from amlodipine to Lotrel (p <0.001).
Amlodipine-induced pedal edema improved in 85% of patients in Group II when they
were switched to Lotrel (p <0.001).
Lotrel was well tolerated. The most commonly occurring side effects were cough
(3.66%), dizziness (1.50%), edema (1.46%) and headache (1.23%).
The full results of this study will be published in the June edition of the
American Journal of Hypertension.
LOGIC presented by: Franz Messerli, MD, Alton Ochsner Medical Foundation, Tulane
University, New Orleans, LA, Friday, May 17, 2002.
ALERT (A Lotrel Evaluation of Hypertensive Patients with ARterial Stiffness and
Left Ventricular HyperTrophy)
Low doses of Lotrel showed greater improvements in arterial compliance and
greater regression of left ventricular mass than higher doses of amlodipine and
benazepril monotherapy.
ALERT is a 26-week, prospective, open-label, blinded endpoint, parallel group
study involving 106 patients with mild to moderate hypertension (DBP of 95-114
mmHg). The study compared the effects of low-dose Lotrel (5 mg/20 mg) versus
high-dose amlodipine (10 mg) and benazepril (40 mg) monotherapy on arterial
stiffness and left ventricular mass.
Patients taking Lotrel experienced significantly greater improvements in
arterial stiffness versus amlodipine and benazepril-treated patients (0.71 +/-
0.51% mL/mmHg vs. 0.28 +/- 0.69% mL/mmHg and 0.39 +/- 0.62% mL/mmHg,
respectively p=0.008, p=0.03). Moreover, patients taking Lotrel had
significantly greater regressions in left ventricular mass index as measured by
echocardiography than amlodipine-treated patients (-29.9 +/- 25.5 g/m2 vs. -14.1
+/- 22.1 g/m2 respectively; p=0.01).
Page 42 of 54 Total Pages
Left ventricular mass index reductions were numerically greater in Lotrel than
in benazepril-treated patients (-19.3 +/- 20.3 g/m2).
These improvements were seen despite the fact that patients on all three
medications achieved similar reductions in systolic and diastolic blood
pressure.
Lotrel was well tolerated. The most commonly occurring side effects were GI
complaints (11.4%), peripheral edema (8.6%), cough (5.7%) and headache (2.8%).
Lotrel is not indicated for the treatment of arterial stiffness or left
ventricular hypertrophy.
ALERT presented by: Joel Neutel, MD, Orange County Heart Institute and Research
Center, Orange County, CA, Saturday, May 18, 2002.
SHIELD (Study of HypertensIon and the Efficacy of Lotrel in Hypertensive
Diabetics)
Patients with diabetes and hypertension taking Lotrel reached their target blood
pressure goal (<135/80 mmHg) 22% faster than those on Vasotec(R) (enalapril)
monotherapy.
SHIELD is a 12-week, randomized, multi-center, double-blind, parallel group
study that evaluated the safety and efficacy of Lotrel versus enalapril
monotherapy in 214 patients with hypertension and type 2 diabetes. ACE inhibitor
treatment with an agent like enalapril is the standard of care for patients with
diabetes. This study was conducted to determine if Lotrel would provide superior
blood pressure control while providing the recommended ACE inhibitor therapy.
Patients in the study with average diastolic blood pressures (DBP) between 90
and 109 mmHg were randomized to either Lotrel 5 mg/10 mg or enalapril 10 mg. If
patients did not reach the target blood pressure of <130/85 mmHg after four
weeks, they were titrated to either Lotrel 5 mg/20 mg or enalapril 20 mg.
Patients not reaching goal after eight weeks received 12.5 mg of
hydrochlorothiazide on top of their treatment regimen.
At the conclusion of the study, patients taking Lotrel reached their target
blood pressure approximately 22% faster than those taking enalapril (5.3 weeks
versus 6.4 weeks respectively, p=0.0001). Moreover, Lotrel-treated patients
experienced significantly greater reductions in systolic blood pressure (SBP)
and DBP than those taking enalapril (-20.5/-13.9 mmHg versus -14.5/-9.6 mmHg
respectively, p =0.002, p =0.001). A statistically significant difference in
reduction in triglyceride levels favoring the Lotrel regimen was also observed
(p=0.039). Lotrel-treated patients experienced a mean decrease in triglycerides
of 21.7 mg/dL, compared with a mean increase of 14.8 mg/dL among
enalapril-treated patients. The changes from baseline in all other lipid levels
were comparable across the treatment groups. There was no negative impact on
glycemic control with either Lotrel or enalapril.
Additionally, a sub-study of 20 SHIELD patients found that Lotrel combination
therapy offered a statistically significant improvement in vascular compliance
(a measure of the arteries' ability to expand and contract with changes in
pressure), over enalapril monotherapy (p<0.05). This improvement occurred
despite the absence of a significant difference in blood pressure between the
groups.
Both Lotrel and enalapril were well tolerated. There were a few reported
incidents of bronchitis, dyspnea, congestive heart failure, angina and foot
ulcers, but none of these was considered to be the result of the study
medication.
Page 43 of 54 Total Pages
SHIELD presented by: George Bakris, MD, Rush University Hypertension Center,
Rush Presbyterian/St. Luke's Medical Center, Chicago, IL, Thursday, May 16,
2002.
SHIELD sub-study presented by: Nathaniel Winer, MD, SUNY Downstate Medical
Center, Brooklyn, NY, Saturday, May 18, 2002.
Ongoing Lotrel Studies
Novartis is conducting clinical studies to further explore the clinical
potential of Lotrel. The LEAAD (Lotrel and Enalapril in African-Americans with
Hypertension and Diabetes) trial is examining the efficacy of Lotrel versus the
ACE inhibitor enalapril on blood pressure reduction and kidney function in
African-Americans with diabetes. Another trial, called SELECT (Systolic
Evaluation of Lotrel Efficacy and Comparative Therapies), is comparing the
effects of Lotrel to amlodipine and benazepril monotherapy on systolic blood
pressure, a critical indicator of cardiovascular risk.
Due to its ACE inhibitor component, Lotrel should be discontinued as soon as
pregnancy is detected because of concerns over its effect on the unborn child.
Also, angioedema, a potentially dangerous swelling of the mouth and throat, has
been reported in patients receiving Lotrel. In clinical trials, the most common
side effects were cough and headache. For full prescribing information, please
consult www.pharma.us.novartis.com.
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 "will be," "will make," "will continue," or similar
expressions, or by discussions regarding potential new indications for existing
products, or the potential outcome of clinical trials. Such forward looking
statements reflect the current views of the Company with respect to future
events and are subject to certain risks, uncertainties and assumptions. There
are no guarantees that any of the potential new indications will be
commercialized in any market, that any additional sales of existing products
will occur as a result of any clinical trial results, or that any of the
aforementioned clinical trials will have any particular result. Any
commercialization of any new indication and any additional sales of existing
products 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 materialize, or should underlying assumptions prove incorrect,
actual results may vary materially from those described herein as anticipated,
believed, estimated or expected.
Vasotec(R) is a registered trademark of Merck & Co. Norvasc(R) is a registered
trademark of Pfizer Inc. The amlodipine active ingredient found in Lotrel is
supplied to Novartis Pharmaceuticals Corporation by Pfizer Inc.
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 44 of 54 Total Pages
[NOVARTIS LOGO] Novartis International AG
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
Starlix(R)enhances glucose control in people with impaired glucose tolerance
New supporting study underlines the rationale for using Starlix in NAVIGATOR,
the largest diabetes prevention trial to date
Basel, 8 May 2002 - New research presented at the World Congress of Cardiology
describes results from the first study to show that Starlix(R) (nateglinide)
enhances early insulin secretion and controls post-prandial blood glucose in
people with impaired glucose tolerance (IGT). This suggests that Starlix may be
a useful agent for controlling post-prandial hyperglycaemia in this pre-diabetic
patient group.
It is estimated that as many as 150 million people may have IGT. People with IGT
show abnormalities in both insulin secretion and response to insulin (insulin
sensitivity), and are at high risk of progressing to type 2 diabetes, with a
40-50% chance of developing the disease within ten years. IGT is an intermediate
state between normal blood glucose control and type 2 diabetes and is
characterised by an excessive rise in blood glucose following an oral glucose
tolerance test. IGT is also a major risk factor for cardiovascular disease.
Dr Leif Groop of the University of Lund in Sweden, one of the study's lead
investigators, commented, "Loss of early insulin secretion is one of the first
pathophysiological signs of progression to type 2 diabetes. By restoring the
normal, physiological pattern of insulin secretion, nateglinide essentially
normalised glucose tolerance in these patients".
The study, which took place at centres in six European countries, involved 288
people with IGT (plasma glucose two hours after consuming 75 g glucose > or =
7.8mmol/l but <11.1 mmol/l and fasting plasma glucose < 7 mmol/l). Subjects were
randomly allocated to take 30 mg, 60 mg, or 120 mg of Starlix (nateglinide), or
a placebo, before main meals for eight weeks. At the start and end of the study,
blood glucose and insulin levels were measured at intervals for three hours
after a standard meal.
The results showed that Starlix (nateglinide) enhanced early insulin secretion
and reduced both the size of the blood glucose peak and the total increase in
blood glucose over the three hours following the meal. Fasting glucose levels
were not affected.
Confirmed hypoglycaemia (plasma glucose levels < or = 3.7 mmol/l) occurred in
five (6.6%) subjects receiving 60 mg nateglinide and 23 (26.7%) of subjects
taking the 120 mg dose. All symptoms were mild and quickly resolved.
Page 45 of 54 Total Pages
"60 mg nateglinide was extremely well tolerated in these IGT patients," remarks
Dr Groop. "The fast-on, fast-off, and glucose-dependent action of nateglinide
means that the risk of hypoglycaemia is minimal, even in these patients who do
not yet have diabetes."
People with IGT are the ideal population to be involved in diabetes prevention
trials. The mode of action of nateglinide and its excellent safety profile have
led to its inclusion in the NAVIGATOR trial launched in November 2001. NAVIGATOR
will be the largest diabetes prevention trial to date, involving 7,500 subjects
in 40 countries, and will determine whether long-term administration of Starlix
(nateglinide) (60 mg before main meals) or the angiotensin II receptor blocker
Diovan(R) (valsartan) (160 mg a day) prevents or delays type 2 diabetes and
cardiovascular disease in people who have IGT and are at high cardiovascular
risk.
Dr Richard Pratley, Medical Director for the NAVIGATOR trial at Novartis Pharma
Corp, East Hanover, USA, explained: "With type 2 diabetes increasing rapidly all
over the world, it is now vital that we explore prevention strategies. This
study demonstrates the clear rationale for including Starlix in the NAVIGATOR
trial. NAVIGATOR will show us whether restoring early insulin secretion with
Starlix can slow decline to type 2 diabetes and prevent cardiovascular disease
in this high-risk group."
Forward-looking statement
The forgoing press release contains forward-looking statements which can be
identified by terminology such as "may be useful", "will be", "will show", or
similar expressions, or by discussions regarding the potential outcome of the
NAVIGATOR clinical trial, or 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 the aforementioned
clinical trials will result in the commercialisation of any product in any
market. Any such commercialisation can be affected by, amongst other things,
uncertainties relating to product development, including the actual outcome of
the NAVIGATOR clinical trial itself, 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.
About Novartis
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 46 of 54 Total Pages
[NOVARTIS LOGO] Novartis International AG
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
Glivec(R)(imatinib)* may be effective in rare blood disease according to new
report in The Lancet
Case report provides additional clinical insight into Hypereosinophilic Syndrome
(HES)
Basel, Switzerland, 3 May 2002 - The Novartis drug Glivec(R) (imatinib)* may
have efficacy in certain patients with hypereosinophilic syndrome (HES),
according to a case report from researchers at the Mayo Clinic and Foundation in
Rochester, Minnesota; and the University of Utah in Salt Lake City, Utah, USA.
The report is published in the 4 May 2002 issue of The Lancet(1).
HES is a very rare group of myeloproliferative disorders of unknown origin,
characterised by the persistent overproduction of eosinophils (a type of white
blood cell that is involved in a variety of functions, including defense against
parasitic infection and allergic responses). HES is most commonly diagnosed in
male patients aged 20-50 years. The symptoms can appear suddenly and
dramatically, and can involve virtually any organ system, but more often they
are insidious. Typically, patients with HES have no detectable chromosomal
abnormality. Notoriously difficult to manage, HES is often treated with the same
therapies used to treat chronic myeloid leukemia (CML). This led the researchers
to hypothesise that HES patients might respond to Glivec, a novel agent that has
demonstrated unprecedented cytogenetic response rates in CML.
"Glivec is a targeted signal transduction inhibitor. Although the mechanism by
which the drug exerts its effects on HES is unclear, Novartis is encouraged by
the preliminary data which suggest that Glivec may play a role in treating these
patients," said David Parkinson, M.D., Vice President, Novartis Oncology.
"Novartis will monitor and investigate potential activity in this area."
Case Report
In the case report, Gleich and colleagues describe five patients, four male and
one female, with clinical manifestations of HES. Glivec was initially
administered to the patients at daily doses of 100 mg--considerably lower than
those dosages required for the treatment of CML and GIST. These findings,
however, do not impact dosing for CML and GIST patients (400 mg to 600 mg/day).
By day seven of treatment with Glivec, four of the five patients had responded.
The fifth patient did not respond to Glivec. However, unlike the other patients,
she had abnormally elevated levels of serum interleukin-5 (IL-5), a cytokine, or
protein, involved in mediating certain immune interactions. The authors suggest
that this finding may help discriminate among patients with HES. The authors
also observed a sixth patient with elevated IL-5 who did not respond to
treatment with Glivec, but they did not report on this patient in detail.
Page 47 of 54 Total Pages
Based on their preliminary findings in this small group of patients, the authors
conclude that Glivec may be effective in male patients with HES and normal
concentrations of IL-5. They also suggest that a tyrosine kinase, similar to
those which Glivec has shown to inhibit, but more sensitive to low doses of the
drug, may be the target that accounts for the observed activity of Glivec in
these patients.
About Glivec
Glivec is a signal transduction inhibitor which inhibits the activity of certain
enzymes, called tyrosine kinases, which play an important role within certain
cancer cells. In CML, for example, it inhibits BCR-ABL, a by-product of the
specific chromosomal abnormality, the Philadelphia chromosome, which
characterises the disease in most patients. In gastrointestinal stromal tumours
(GISTs), Glivec has been shown to inhibit the c-kit tyrosine kinase, and In
vitro, Glivec has also been shown to inhibit PDGF-R (platelet derived growth
factor receptors). Novartis is investigating the efficacy of Glivec, alone and
in combination with other therapies, in a range of diseases in which these
tyrosine kinases play a role.
In most countries where it is approved, Glivec is indicated for the treatment of
patients with Philadelphia chromosome-positive CML in the blast crisis,
accelerated phase or in chronic phase after failure of interferon-alpha therapy.
The effectiveness of Glivec is based on overall haematological and cytogenetic
response rates.
Glivec has been approved for the CML indication in the United States, the
European Union and more than 60 countries. In the U.S. and in Switzerland, it is
approved for the treatment of patients with Kit (CD 117) positive unresectable
(inoperable) and/or metastatic malignant gastrointestinal stromal tumours
(GISTs). The Committee for Proprietary Medicinal Products (CPMP) in the EU
issued a positive opinion for the GIST indication in February 2002, and approval
is expected shortly.
Contraindications and Adverse Events
The majority of patients treated with Glivec experience adverse events at some
time. Most events are of mild to moderate grade, but in clinical trials for CML
the drug was discontinued for adverse events in 2% of patients in chronic phase,
3% in accelerated phase and 5% in blast crisis. Women of childbearing potential
should be advised to avoid becoming pregnant while taking Glivec. The most
common side effects included nausea, fluid retention, vomiting, diarrhoea,
haemorrhage, muscle cramps, skin rash, fatigue, headache, dyspepsia and
dyspnoea, as well as neutropenia and thrombocytopenia. Serious and severe side
effects, such as hepatotoxicity (1% to 4%), fluid retention syndrome (3% to
12%), neutropenia (8% to 48%) and thrombocytopenia (less than 1% to 33%) have
also been reported in some patients. There are no long-term safety data on
Glivec treatment available up to now.
The foregoing release contains forward-looking statements that can be identified
by terminology such as "encouraged," "may be the target," "may play a role" and
"may be effective," 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 Health
Authorities' further requirements is not guaranteed and management's
expectations regarding further commercialisation 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
Page 48 of 54 Total Pages
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 materialise, or should underlying assumptions prove
incorrect, actual results may vary materially from those anticipated, believed,
estimated or expected.
About Novartis
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. Gleich GJ, Leiferman, KM, Pardanani, A. Tefferi, A. Butterfield, JH. (2002)
Treatment of hypereosinophilic syndrome with imatilib mesylate. The Lancet,
04 May 2002.
# # #
Page 49 of 54 Total Pages
[NOVARTIS LOGO] Novartis International AG
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
Interim data from MO2ART study using Neoral(R) C2 monitoring demonstrates
impressive, low rates of kidney rejection
Basel, 2 May 2002 - Neoral(R) C2 monitoring results in acute organ rejection
rates of only 10% in kidney transplant patients, according to interim data of
the MO2ART study. The findings were presented at the third joint annual meeting
of the American Society of Transplant Surgeons and the American Society of
Transplantation as part of the American Transplant Congress (ATC) held in
Washington, DC.
"This is the lowest rate of acute rejection ever demonstrated with
cyclosporin-based triple therapy in a multicentre international trial" said Dr.
Paul Keown, University of British Columbia. "These data underscore my belief
that individualizing patient immunosuppression will be the future in organ
transplantation management."
MO2ART (Monitoring Of 2-hour Neoral Absorption in Renal Transplantation),
sponsored by Novartis, is the first prospective, randomized, international study
designed to evaluate the clinical benefit of Neoral C2 patient management in
kidney transplantation. The MO2ART study will also help to determine the optimum
Neoral C2 levels for maintenance therapy. This open label 12-month trial is
being conducted in 30 centers in 10 countries. All transplant patients received
triple immunosuppression - Neoral (cyclosporin for microemulsion), steroids,
mycophenolate mofetil (MMF) / azathioprine. Interim analyses were performed when
117 of the 290 patients completed three months on the study.
"Today, organ transplantation is very successful, yet we can still do more in
terms of reducing acute rejection following transplantation," said Tony
Rosenberg, Global Head of Transplant and Immunology Business Unit, Novartis
Pharma AG. "These primary results suggest that Neoral C2 monitoring is a cutting
edge patient management technique that may assist clinicians in individualizing
therapy to optimize patient outcomes."
Interim results of the MO2ART study demonstrate impressive, low levels of acute
rejection both in patients with immediate graft function (IGF) and in those
experiencing delayed graft function (DGF). Specifically:
o The Acute Rejection (AR) rate* within the current trial population (n=117)
was 10%
o The AR rate* within the IGF group (n=70) was 6%
o The AR rate* within the DGF group (n=47), who are at increased risk of AR*,
was also very low at 16%
(*AR was measured as BPAR - Biopsy Proven Acute Rejection)
"I think that these results demonstrate that monitoring of Neoral therapy using
C2 is an effective, safe and simple tool for optimizing patient therapy and
achieving low levels of acute organ rejection," said Professor Bjorn Nashan at
the Clinic for Visceral and Transplantation surgery in Hannover, Germany. "We
will continue to watch the MO2ART study evolve with great interest."
Page 50 of 54 Total Pages
In this interim analysis, safety and tolerability were excellent. The proportion
of patients experiencing cyclosporin-related acute renal dysfunction was 5%.
Median serum creatinine at month 3 was 129 (mu)mol/L for IGF and 133 (mu)mol/L
for DGF patients, demonstrating excellent renal function even in the DGF
population. Also, there were only seven serious adverse events related to
cyclosporin.
These results, based on a three-month interim analysis, provide support that:
o C2 monitoring is an effective, safe and simple tool for optimizing Neoral
therapy, achieving low levels of acute rejection in renal transplantation.
o Achieving early target C2 exposure is associated with very low incidence
of acute rejection with excellent renal tolerability.
What is Neoral C2 monitoring?
Neoral C2 monitoring is a patient management tool which involves making Neoral
dose adjustments based on a measurement of the concentration of cyclosporin in a
patient's blood two hours (C2) post-dose as opposed to the traditional practice
of trough level (C0) monitoring - immediately before drug intake. This allows
clinicians to individualize therapy according to drug absorption characteristics
of each patient, which may then reduce the risks for acute rejection and
cyclosporin toxicity. Ultimately, this may result in marked improvements in the
efficacy and safety of Neoral.
Neoral, introduced in 1995, is indicated for the prophylaxis of organ rejection
in kidney, liver and heart allogeneic transplants, and continues to be a
cornerstone of immunosuppressive therapy. Neoral is contraindicated in patients
with a hypersensitivity to cyclosporin or any ingredients in its formulation.
Only physicians experienced in the management of systemic immunosuppressive
therapy for the indicated disease should prescribe Neoral. Neoral may be
administered with other immunosuppressant agents.
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 "demonstrates," "determines," "cutting-edge," "support,"
"may" or similar expressions, or by discussions of strategy, plans or
intentions. Such statements include descriptions of the potential benefit of
Neoral as evidenced by the results of clinical studies. Those 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 and Neoral 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 the aforementioned study will result in the increased sales of
Neoral in any market. Any such commercialisation can be affected by, among other
things, additional analysis of data, new data, 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, competition in general and other risks and factors referred
to in the Company's current Form of 20-F on file with the Securities and
Exchange commission of the United States.
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 51 of 54 Total Pages
[NOVARTIS LOGO] Novartis International AG
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 broadens horizons in post-transplant immunosuppression:
FTY720 plus CerticanTM shows efficacy and safety in a calcineurin inhibitor
(CNI) - free regimen
Basel, 2 May 2002 - Organ transplant patients may soon be able to benefit from a
promising alternative to standard calcineurin inhibitor (CNI) based
immunosuppressive regimens1, according to a new study presented at this year's
American Transplant Congress (ATC).
The multicentre, prospective Phase II study of 52 kidney transplant patients at
high risk of delayed graft function (DGF) showed that a combination of the
Novartis investigational agents FTY720 (a lymphocyte-homing agent which
reversibly redirects lymphocytes away from the graft) and CerticanTM (a
proliferation inhibitor which targets primary causes of chronic rejection),
together with standard corticosteroids, achieved immunosuppressive efficacy
comparable to that seen with CNI-based regimens, without the risk of
nephrotoxicity often associated with CNI use.
Lead investigator Dr Marc I. Lorber, Professor of Surgery and Chief, Section of
Organ Transplantation and Immunology at the Yale University School of Medicine,
commented: "The patients in this study were all at high risk of experiencing
delayed graft function2, a situation associated with a deleterious effect on
ultimate graft survival3. To that end, they represented a particularly
vulnerable group. Nonetheless, the incidence of graft loss and acute rejection
seen to date compared favourably with the rates usually seen with more
conventional CNI-based regimens in this difficult patient population.
Importantly, the FTY720 / CerticanTM regimen resulted in good renal function in
these high risk patients, with serum creatinine levels comparable to those
expected in a low risk group. This approach may offer a viable alternative to
CNI-based immunosuppression among patients at risk of DGH, possibly representing
an important immunosuppression strategy for these high risk patients."
FTY720 is a completely novel therapeutic agent with a highly selective mode of
action. Through its targeted lymphocyte homing activity, FTY720 is expected to
protect the graft from T-cell mediated damage, while leaving other aspects of
the immune response unimpaired and thus still able to ward off systemic
infections. Pre-clinical studies have shown that the host's response to
infectious challenge is not impaired by FTY720.
Furthermore, in clinical trials, treatment with FTY720 was associated with a low
incidence of regimen-related adverse events. A negative chronotropic effect
(bradycardia4) has been observed previously in patients being treated with
FTY720, and in this study was reported in 10% of patients. Bradycardia
associated with FTY720 treatment is generally transient, mild, and recovers
spontaneously in the majority of patients.
Page 52 of 54 Total Pages
In a second FTY720 clinical study presented at this year's ATC, it was
demonstrated that, in contrast to most other immunosuppressants, therapeutic
drug monitoring is not required during FTY720 administration, potentially
increasing ease of use for the patient and the physician.
Novartis is currently exploring further the possibility of CNI-free regimens in
animal models. A study of the combination of FTY720 with MyforticTM - a
gastroprotective formulation of the immunosuppressant mycophenolic acid - was
shown to be promising and to merit further investigation.
"FTY720 is being actively investigated in renal transplant patients and
accumulating results suggest this agent may represent an important advance in
our efforts to provide more effective, better tolerated and safer
immunosuppression", Dr Lorber said.
With its broad portfolio of developmental products, Novartis is continuing to
shape the future of transplantation.
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 "to broaden horizons", "may soon be able to benefit from a
promising alternative", "potentially increasing", "may represent an important
advance", or similar expressions, or by or by discussions regarding the
potential development of new products. Such statements include descriptions of
Novartis' transplantation products either on the market or under development by
the Company. 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 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 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 the Company's Form 20-F 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 72,600 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
# # #
NOTES TO EDITORS
1. Calcineurin inhibitor (CNI) based regimens are those based on cyclosporin
or tacrolimus. Neoral(R) (cyclosporin microemulsion) is the most widely
prescribed immunosuppressant in the world and the cornerstone of treatment
in transplant recipients.
2. Patients were selected on the basis of having a DGF probability of 50% or
more using a DGF risk index developed specifically for this study.
3. In kidney transplant patients with good early graft function, graft
survival six months post-transplant is typically 96% but this falls to 82%
in those with delayed graft function (DGF).
4. Bradycardia = slowing of the heart rate
Page 53 of 54 Total 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: June 6, 2002 By: /s/ MALCOLM B. CHEETHAM
--------------------------------
Name: Malcolm B. Cheetham
Title: Head Group Financer
Group Fin. Reporting and Accounting
Page 54 of 54 Total Pages