Genzyme launches test to monitor Gleevec resistance

Genzyme Corporation has announced the availability of an important new test to monitor drug resistance in chronic myeloid leukemia (CML) patients who are treated with Gleevec (imatinib mesylate).

Despite high response rates to Gleevec, approximately four to five percent of patients who were initially treated successfully will develop resistance during therapy. Genzyme's new BCR-ABL Mutation Analysis test will assist physicians in evaluating resistance to therapy and facilitate appropriate adjustments to treatment.

The molecular hallmark of CML is a mutation known as BCR-ABL. This mutation is the specific target for Gleevec and is found in 95 percent of patients with CML. In relapse patients, the majority of secondary mutations in the ABL portion of the gene correlate with treatment failure. Genzyme's new test detects all secondary BCR-ABL mutations and therefore predicts resistance to Gleevec.

"This is a very exciting time for leukemia patients and their caregivers because this test will provide them with more information about their disease and will give them the ability to personalize their treatment," said Mara Aspinall, president of Genzyme Genetics, the business unit of Genzyme Corp. focused on the research and development of high quality, complex testing services.

"We are pleased to offer another important predictive test that can play a critical role in the way oncologists and patients manage their cancer," she added. Genzyme recently launched several other personalized medicine tests in the areas of lung cancer and leukemia and lymphoma.

Because of its high efficacy and limited side effects, Gleevec as a first- line therapy is considered to have revolutionized long-term survival of patients with CML. Gleevec was approved by the U.S. Food and Drug Administration in May, 2001 as the first drug in a new class of molecular targeted therapies for CML. Over 90 percent of patients treated with Gleevec respond initially to treatment, and many experience a complete remission. However, four to five percent of these patients eventually develop resistance to the treatment and experience a relapse of their disease.

The discovery of the BCR-ABL mutations was made by researchers at the University of California at Los Angeles (UCLA) Jonsson Cancer Center in 2001, who are currently working to determine if the same mutations in patients with CML may also lead to resistance to newer investigational treatments.

In October, Genzyme announced that it entered into a license agreement with UCLA to obtain exclusive, worldwide diagnostic rights to UCLA's discovery of gene mutations believed to be associated with drug resistance to Gleevec.

Genzyme Genetics offers two tests that identify non-small cell lung cancer (NSCLC) patients likely to respond to therapies. The presence of epidermal growth factor receptor (EGFR) mutations have been shown to correlate with clinical response to certain drugs, including Tarceva (erlotinib) and IRESSA (gefitinib), used in treating this deadly form of cancer. Genzyme now offers EGFR by FISH (fluorescence in-situ hybridization), which detects over amplification of the EGFR gene. This new test complements Genzyme's EGFR Mutation Assay, which also detects the presence of EGFR in patients with NSCLC.

Genzyme has also made available a new assay that detects a mutation in the Janus kinase 2 (JAK2) gene common in chronic myeloproliferative disorders (MPDs). MPDs are a large group of pathogenetically related diseases (including CML) characterized by proliferation of one or more myeloid cell lines in the bone marrow and increased numbers of mature and immature cells in the peripheral blood diseases. This new JAK2 test allows for the classification, diagnosis, and potential treatment of these diseases.

Chronic myeloid leukemia is also known as chronic myelogenous leukemia. According to the American Cancer Society, CML is a type of cancer that starts in blood-forming cells of the bone marrow and then invades the blood. It can spread to the lymph nodes, spleen, liver, and other parts of the body. CML can also change into a fast-growing acute leukemia that invades almost any organ in the body.

The American Cancer Society estimated that there were approximately 4,600 new cases of CML diagnosed in 2005. Approximately 25,000 CML patients are living in remission on therapy in the U.S. today. The average age of people with CML is around 50 years.