Novartis completes submissions in US and Europe for Gleevec(R) as treatment for four rare types of cancer

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Subject: Novartis completes submissions in US and Europe for Gleevec®

as treatment for four rare types of cancer

Press ReleaseSource: Novartis Pharmaceuticals Corporation

Novartis completes submissions in US and Europe for Gleevec® as

treatment

for four rare types of cancer

Monday April 10, 1:15 am ET

* Research program based on Gleevec-sensitive pathways in multiple rare

disorders exemplifies future direction of targeted cancer diagnosis and

treatment

* Regulatory submissions reflect continued commitment to identifying new

therapies for patients with rare diseases who have limited treatment

options

EAST HANOVER, N.J., April 10 /PRNewswire/ -- Novartis announced today

that

it has submitted applications in the United States and Europe for

GleevecR

(imatinib mesylate)* tablets as treatment for four rare types of cancer.

These filings underscore how cancers of different origin and location

can

share common pathways that respond to the same targeted treatment.

" Thanks to the success of targeted therapies like Gleevec, these filings

speak to the fundamental shift that we are seeing in the approach to

cancer

treatments, " said Diane Young, Vice President and global head of

Clinical

Development at Novartis Oncology. " One day, cancer may no longer be

classified by site, or even by single genes or proteins, but instead by

the

way in which the cancer is expressed. This could potentially give rise

to

more targeted treatment options such as Gleevec. "

Gleevec targets the activity of proteins called tyrosine kinases that

play

important roles within some cancer cells. Gleevec has been shown to

inhibit

the function of the tyrosine kinase Bcr-Abl in Philadelphia-chromosome

positive (Ph+) chronic myeloid leukemia (CML), and the receptor tyrosine

kinase Kit in Kit (CD117)-positive gastrointestinal stromal tumors

(GIST).

Researchers have found that Gleevec also inhibits other receptor

tyrosine

kinases, including platelet-derived growth factor (PDGFR), that have

been

shown to be activated in disease pathways that underlie a number of rare

hematologic diseases, as well as some solid tumors.

The diseases found to have Gleevec-sensitive pathways include the solid

tumor dermatofibrosarcoma protuberans (DFSP), a type of tumor that

begins as

a hard lump found in the skin of the chest, abdomen or leg. Three

hematologic diseases were also found: certain forms of

myeloproliferative

disorders (MPD), diseases in which too many types of certain blood cells

are

made in the bone marrow; hypereosinophilic syndrome (HES), which is

characterized by the persistent overproduction of the white blood cells

eosinophils; and systemic mastocytosis(SM), which is marked by the

presence

of too many mast cells, a certain type of white blood cell. These

diseases

are rare but may be life threatening. For many of the patients who

suffer

from them, no approved treatment is available. Novartis submitted the

marketing applications in Europe and the United States for DFSP and MPD

in

2005, and for SM and HES in 2006.

The submissions are based on a Novartis-sponsored clinical study and

clinical data from trials done by independent medical researchers and

cooperative trial groups demonstrating efficacy and safety of Gleevec in

the

treatment of these different rare diseases.

About Gleevec Tablets

Gleevec (imatinib mesylate) tablets are indicated for the treatment of

newly

diagnosed adult patients with Philadelphia chromosome-positive (Ph+)

chronic

myeloid leukemia (CML) in chronic phase. Follow-up is limited. Gleevec

tablets are also indicated for the treatment of patients with Ph+ CML in

blast crisis, in accelerated phase, or in chronic phase after failure of

interferon-alpha (IFN-alpha) therapy. Gleevec tablets are also indicated

for

the treatment of pediatric patients with Ph+ chronic phase CML whose

disease

has recurred after stem cell transplant or who are resistant to

IFN-alpha

therapy. There are no controlled trials in pediatric patients

demonstrating

a clinical benefit, such as improvement in disease-related symptoms or

increased survival. Gleevec tablets are also indicated for the treatment

of

patients with KIT (CD117)-positive unresectable and/or metastatic

malignant

gastrointestinal stromal tumors. The effectiveness of Gleevec is based

on

objective response rate. There are no controlled trials demonstrating a

clinical benefit, such as improvement in disease-related symptoms or

increased survival.

Important Safety Information(1)

Severe (NCI Grades 3/4) neutropenia (3%-48%), anemia (<1%-42%),

thrombocytopenia (<1%-33%), hemorrhage (1%-19%), fluid retention (eg,

pleural effusion, pulmonary edema, and ascites <1%-8%) and superficial

edema

(1%-6%), musculoskeletal pain (1%-9%), and hepatotoxicity (3%-8%) were

reported among GleevecR recipients. Patients should be weighed and

monitored

regularly for signs and symptoms of edema, which can be serious or

life-threatening. There have also been reports, including fatalities, of

cardiac tamponade, cerebral edema, increased intracranial pressure,

papilledema, and gastrointestinal perforation.

Bullous dermatologic reactions (eg, erythema multiforme and

s-

syndrome) have also been reported. In some cases, the reaction recurred

upon

rechallenge. Several foreign postmarketing cases note a resolution or

improvement of bullous reaction following dose reduction with or without

supportive care.

Dose adjustments may be necessary due to hepatotoxicity, other

nonhematologic adverse events, or hematologic adverse events. Therapy

with

Gleevec was discontinued for adverse events in 3% to 5% of patients.

Patients with severe hepatic impairment should be treated at a starting

dose

of 300mg/day and should be closely monitored.

Gleevec is metabolized by the CYP3A4 isoenzyme and is an inhibitor of

CYP3A4, CYP2D6, and CYP2C9. Dosage of Gleevec tablets should increase by

at

least 50% and clinical response should be carefully monitored in

patients

receiving Gleevec tablets with a potent CYP3A4 inducer such as rifampin

or

phenytoin. Examples of commonly used drugs that may significantly

interact

with Gleevec include acetaminophen, warfarin, erythromycin, and

phenytoin.

Please see enclosed full prescribing information for other potential

drug

interactions.

For daily dosing of 800mg and above, dosing should be accomplished using

the

400mg tablets to reduce exposure to iron.

Use of Gleevec tablets is contraindicated in patients with

hypersensitivity

to imatinib or to any other component of Gleevec tablets.

Women of childbearing potential should be advised to avoid becoming

pregnant

while taking Gleevec tablets.

Because of the potential for serious adverse reactions in nursing

infants,

women should be advised to avoid breast-feeding while taking Gleevec

tablets.

Common Side Effects of Gleevec Tablets(2)

The majority of the approximately 1700 adult patients who received

Gleevec

in clinical studies experienced adverse events at some time, but most

were

mild to moderate in severity. The most frequently reported adverse

events

were superficial edema (58%-81%), nausea (47%-74%), diarrhea (39%-70%),

muscle cramps (28%-62%), vomiting (21%-58%), rash (36%-53%), fatigue

(30%-53%), musculoskeletal pain (30%-49%), and abdominal pain

(30%-40%).*

Supportive care may help management of most mild-to-moderate adverse

events

so that prescribed dose can be maintained whenever possible.

Gleevec tablets should be taken with food and a large glass of water to

minimize gastrointestinal (GI) irritation. Gleevec tablets should not be

taken with grapefruit juice.

The foregoing release contains forward-looking statements that can be

identified by terminology such as " continued commitment, " " one day, "

" may, "

" could potentially, " " may be " or similar expressions, or by express or

implied discussions regarding potential new indications for Gleevec or

potential future sales of Gleevec, or regarding the long-term impact of

a

patient's use of Gleevec. Such forward-looking statements involve known

and

unknown risks, uncertainties and other factors that may cause actual

results

with Gleevec to be materially different from any future results,

performance

or achievements expressed or implied by such statements. There can be no

guarantee that Gleevec will be approved for any additional indications

in

any market. Nor can there be any guarantee regarding potential future

sales

of Gleevec. Neither can there be any guarantee regarding the long-term

impact of a patient's use of Gleevec. In particular, management's

expectations regarding commercialization of Gleevec could be affected

by,

among other things unexpected clinical trial results, including new

clinical

trial results and additional analysis of existing 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; government,

industry, and general public pricing pressures; and other risks and

factors

referred to in the Company's current Form 20-F on file 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 anticipated, believed,

estimated or expected. Novartis is providing this information as of this

date and does not undertake any obligation to update any forward-looking

statements contained in this document as a result of new information,

future

events or otherwise.

About Novartis

Novartis Pharmaceuticals Corporation researches, develops, manufactures

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 - News) -- a world leader in

pharmaceuticals and consumer health. In 2005, the Group's businesses

achieved sales of USD 32.2 billion and pro forma net income of USD 6.1

billion. The Group invested approximately USD 4.8 billion in R & D.

Headquartered in Basel, Switzerland, Novartis Group companies employ

approximately 91,000 people and operate in over 140 countries around the

world. For further information please consult http://www.novartis.com.

* Known as GlivecR (imatinib) outside of the U.S.

(1) GleevecR (imatinib mesylate) tablets prescribing information.

East

Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.

(2) GleevecR (imatinib mesylate) tablets prescribing information.

East

Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.

Media only: Investors only:

Kim Fox Jill Pozarek

Novartis Oncology Novartis Corporation

P: 1 862-778-7692 P: 1 212-830-2445

F: 1 773-781-2074

Dana Kahn

P: 1 732-817-1800

F: 1 732-817-1834

Veronique Boissonnas

Ruder Finn

P: 1 212-593-6396

F: 1 212-583-2702

Source: Novartis Pharmaceuticals Corporation