Healthcare Industry News:  systemic mastocytosis 

Biopharmaceuticals Oncology

 News Release - April 10, 2006

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

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 (HSMN NewsFeed) -- Novartis announced today that it has submitted applications in the United States and Europe for GleevecŪ (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 GleevecŪ 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 Stevens-Johnson 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 ) -- 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 GlivecŪ (imatinib) outside of the U.S.

(1) GleevecŪ (imatinib mesylate) tablets prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.

(2) GleevecŪ (imatinib mesylate) tablets prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2005.


Source: Novartis Pharmaceuticals

Issuer of this News Release is solely responsible for its content.
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