~ Breakthrough cancer drug targets enzyme thought to drive growth and division of GISTs ~
DORVAL, Quebec (December 5, 2001) --Novartis Pharmaceuticals Canada Inc. announced today that Health Canada has granted a Priority Review to its novel drug Gleevec® (imatinib mesylate) for the treatment of patients with unresectable (inoperable) and/or metastatic malignant gastrointestinal stromal tumours (GISTs). Priority Review status is granted to a drug that is intended to treat life-threatening diseases, and that provides an effective treatment of a disease for which no drug is currently marketed in Canada.
GISTs are the most common malignant form of sarcoma arising in the gastrointestinal tract. Historically, GISTs have been very difficult to treat due to their high levels of resistance to treatment with traditional chemotherapy and radiation therapy. For patients with metastatic or unresectable disease, GISTs represent an incurable malignancy with a median survival of approximately ten to twelve months. Until now, surgery has been the only treatment option, resulting in essentially palliation of this disease.
"GISTs are very difficult to treat and there are very few options beyond surgery for these patients," said Dr. Beat Sümegi, Vice President - Medical Affairs. "Gleevec® is extremely active against the molecular abnormality that helps trigger GISTs, and we believe it represents a significant advance in overall treatment of the disease."
Gleevec® Background
Gleevec® was approved on September 20, 2001 for the treatment of patients with chronic myeloid leukemia (CML) in the blast crisis, accelerated phase or in chronic phase after failure of interferon-alpha therapy. Specifically, a Notice of Compliance with Conditions (NOC-C) was granted. The NOC-C allows the approval of drugs for serious or life-threatening illnesses based on clinical trials that establish that the drug has a positive effect on surrogate endpoints that reasonably predict clinical benefit. The effectiveness of Gleevec® in CML is based on overall hematologic and cytogenetic response rates. Long-term safety data are not available and drug interaction data are limited. Confirmatory studies with Gleevec® are ongoing. To date, Gleevec® in CML has been approved in over 30 countries, including the United States.
About Gleevec® and GISTs
The submission for approval from Health Canada is supported by data from a Phase II, open-label, multinational study conducted in 147 patients with unresectable or metastatic malignant GIST. Patients were randomized to receive either 400 mg or 600 mg of Gleevec® daily for up to 24 months. The overall response rate is 40% based on confirmed partial responses at the time of the data cut-off for the submission. An additional 32% of patients in this study achieved a clinically significant reduction in tumor size. Only 12% of patients progressed in the study.
Contraindications and Adverse Events
Gleevec® is one of the first cancer drugs to be developed using rational drug design, based on an understanding of how some cancer cells work. Gleevec® targets the activity of certain enzymes called tyrosine kinases that play an important role within certain cancer cells. The activity of one of these tyrosine kinases, known as c-kit, is thought to drive the growth and division of most GISTs.
Gleevec® has been well tolerated in patients with GIST. Although almost all patients had adverse events reported at least once during the trial, only a very small percentage had these recorded as either grade 3 or 4 in severity. Five patients (3.4%) withdrew from the study due to adverse events. In this clinical trial, the most common adverse events were nausea; diarrhea; periorbital edema; fatigue; muscle cramps; abdominal pain; dermatitis; vomiting; flatulence; lower limb edema; nasopharyngitis; insomnia; back pain; and pyrexia. The adverse events in patients with GIST are similar to those in patients with CML, and the majority of CML patients treated with Gleevec® also experienced adverse events at some time. Most events were of mild to moderate grade, but drug was discontinued for adverse events in 1% of patients in chronic phase, 2% in accelerated phase and 5% in blast crisis. Gleevec® is contraindicated in patients with known hypersensitivity. Women of childbearing potential should be advised to avoid becoming pregnant. If Gleevec® is used during pregnancy or if the patient becomes pregnant while taking Gleevec®, the patient should be apprised of the potential hazard to the fetus. The most common side effects included nausea, fluid retention, muscle cramps, diarrhea, vomiting, hemorrhage, musculoskeletal pain, skin rash, headache, fatigue, arthralgia, dyspepsia and dyspnea. Serious and severe side effects, such as hepatoxicity (1.1% to 3.5%), fluid retention syndrome (2%to 10%), neutropenia (8% to 46%) and thrombocytopenia (less than 1% to 31%) have also been reported in some patients. There are no long-term safety data on Gleevec® treatment.
Forward-Looking Statements
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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, 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 (NYSE:NVS)
Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well being of all Canadians. Novartis Pharmaceuticals Canada conducts hundreds of clinical trials across the country seeking new treatments for cardiovascular disease, diabetes, cancer, organ transplantation and glaucoma. In 2000, the Company invested close to $34 million in research and development. Novartis Pharmaceuticals Canada Inc. employs over 600 people in Canada and its headquarters are located in Dorval, Quebec.
In addition to Novartis Pharmaceuticals Canada Inc., the Novartis Group in Canada consists of Novartis Animal Health Canada Inc., Novartis Consumer Health Canada Inc., (including Novartis Nutrition Corporation) and CIBA Vision Canada Inc. Worldwide in 2000, the Novartis Group's ongoing businesses achieved sales of $25.5 billion and a net income of $5.7 billion. The Group invested approximately $3.5 billion in R&D. Headquartered in Basel, Switzerland, Novartis employs about 70,000 people and operates in over 140 countries around the world.
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