~ Data Comparing Gleevec® to Interferon Combination Therapy Presented at American Society of Clinical Oncology Annual Meeting ~
MONTREAL, Quebec (May 24, 2002) -- Data from the first ever
head-to-head study of the Novartis drug Gleevec® (imatinib mesylate)
demonstrate that Gleevec® 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 (IFN+Ara-C), a form of chemotherapy. In addition,
Gleevec® significantly delayed the time to progression to the
more advanced stages of CML, compared with IFN+Ara-C. These new data were presented
at the 2002 meeting of the American Society of Clinical Oncology (ASCO) in Orlando,
Florida. Gleevec® is a novel therapy that offers a new treatment
option to patients suffering from CML, a disease that previously had limited
treatment options. It also has provided researchers with new insights into the
biological mechanisms of cancer.
In September of 2001, Health Canada approved Gleevec®, an oral therapy for the treatment of CML in blast crisis, accelerated phase or chronic phase after failure of interferon-alpha therapy. Gleevec®, a signal transduction inhibitor, is one of the first cancer treatments to be developed using rational drug design, based on an understanding of how some cancer cells work. Gleevec® targets an abnormal tyrosine kinase that is present in a majority of patients with CML. The effectiveness of Gleevec® in CML is based on overall hematologic and cytogenetic response rates.
"The results clearly show that the earlier Gleevec® is used in treating CML, the better the response," said Dr. Pierre Laneuville, Director of the Division of Hematology at McGill University Health Centre. "These data are so supportive of using Gleevec® in patients newly-diagnosed with CML that physicians need to strongly reconsider the current treatment options for CML patients."
CLINICAL DATA
The International Randomized Study of Interferon vs. STI571 (IRIS) is an open-label Phase III trial that enrolled 1,106 patients in 177 centres across 16 countries. There were two arms to the study: the patients in one arm received Gleevec® at 400 mg/day orally, those in the other arm received IFN by subcutaneous injection at a target dose of 5 MIU/M2/day with Ara-C 20 mg/M2/day by subcutaneous injection for 10 days each month. The results presented were based on data collected up to 12 months after the last patient was randomized; median follow-up was 14 months. The results showed that patients taking Gleevec® had achieved major [Philadelphia Chromosome positive cells, (Ph+) =35%] and complete (0% Ph+ cells) cytogenetic responses of 84% and 69%, compared with patients in the IFN+Ara-C arm, who experienced major and complete cytogenetic responses of 30% and 11.5%, respectively. The complete hematologic response rates were 96% for the Gleevec® arm and 67% for the IFN+Ara-C arm.
Last January, based on the outcome of a planned interim analysis of the six-month results, an Independent Data Monitoring Board (IDMB) requested a change in the study protocol that enabled patients receiving IFN+Ara-C to switch to Gleevec® if they had not achieved a major cytogenetic response after 12 months of therapy, instead of 24 months originally stipulated by the protocol. The option to switch to the alternative treatment was also offered to Gleevec®-treated patients. The protocol change also allowed, upon request, patients receiving IFN+Ara-C to switch to Gleevec®. At the time of this analysis, fewer than 1% of Gleevec®-treated patients crossed over to the IFN+Ara-C therapy, compared with 39% of IFN+Ara-C-treated patients who crossed over to Gleevec® due to insufficient efficacy or intolerance.
In the study, patients taking Gleevec® 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 Gleevec® arm, compared with 80.3% in patients randomized 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 hematologic 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 higher in the Gleevec® arm (98.5%), compared to the IFN+Ara-C arm (93.1%), regardless of crossover.
The safety profile with Gleevec® was similar to that of previous Phase II studies. The most frequent adverse events with Gleevec® were mild to moderate superficial edemas, muscle cramps, skin rash and nausea. The most frequent adverse events with IFN+Ara-C were nausea, fatigue, headache and diarrhea. In the Gleevec® arm, only 2% and 0.7% of patients discontinued from the study or crossed over to the alternative arm for safety reasons respectively. 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 characterizes most cases of CML; it is the result of the transfer of DNA between chromosomes 9 and 22. Cytogenetic response, regarded as a major 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 (by metaphase analysis).
This study was one of several posters and presentations about Gleevec® and CML at the ASCO meeting. Results presented from these studies include data in newly diagnosed Ph+ chronic phase CML patients, and preliminary data from a CML dosing study and cost effectiveness analysis.
CONTRAINDICATIONS AND ADVERSE EVENTS
In the second-line treatment of CML patients following failure of interferon-alpha therapy, the majority of patients treated with Gleevec® experienced adverse events at some point. Most events are of mild to moderate grade, however, the results from the Phase II clinical trials that formed the basis of the CML submission, demonstrated that the drug was discontinued for adverse events in 1% of patients in chronic phase, 2% in accelerated phase and 5% in blast crisis. The most frequently reported drug-related adverse events included mild nausea, vomiting, diarrhea, myalgias and muscle cramps. Serious and severe side effects, such as hepatotoxicity (1% to 5%), fluid retention (1% to 2%), neutropenia (8% to 47%) and thrombocytopenia (less than 1% to 33%) have also been reported in some patients. There are no long-term safety data on Gleevec® treatment beyond 12 months.
Women of childbearing potential should be advised to avoid becoming pregnant while taking Gleevec®. Use of Gleevec® is contraindicated in patients with hypersensitivity to imatinib and to any other component of Gleevec®.
The foregoing release contains forward-looking statements that can be identified by terminology such as "nearly three times more effective," and "new insights" or similar expressions. 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. In particular, management's ability to ensure satisfaction of Health Canada's further requirements (under the Notice of Compliance with Conditions policy) is not guaranteed and management's expectations regarding further commercialization of Gleevec® could be affected by, among other things, additional analysis of data; new data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the Company's ability to obtain or maintain patent or other proprietary intellectual property protection and competition in general. 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 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 2001, the Company invested $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 2001, the Novartis Group's businesses achieved sales of $28.6 billion and a net income of $6.3 billion. The Group invested approximately $3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis employs about 71,000 people and operates in over 140 countries around the world.
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