Genzyme licences rights to leukaemia markers

Genzyme has entered into a licence agreement with the University of California at Los Angeles (UCLA) Jonsson Cancer Center to obtain exclusive, worldwide diagnostic rights to its discovery of gene mutations believed to be associated with drug resistance to Gleevec (imatinib mesylate), the current first-line therapy for patients with chronic myeloid leukaemia (CML).

The molecular hallmark of CML is a mutation known as BCR-ABL, the specific target for Gleevec, found in 95% of patients. Secondary mutations in the ABL portion of the gene correlate with treatment failure or relapse in most patients on Gleevec therapy.

Through the licence, Genzyme will be the first company to develop and market a diagnostic test to detect a significant portion of these secondary BCR-ABL mutations and monitor resistance in CML patients prior to, and during, treatment with Gleevec. Results from such a test may assist physicians in predicting patient relapse and making appropriate adjustments in treatment.

Because of its high efficacy and mild morbidity, Gleevec, as a first-line therapy, is considered to have 'revolutionised long-term survival' of patients with CML. It was approved by the US FDA in May 2001 as the first drug in a new class of anti-neoplastic agents for the treatment of CML, and over 90% of patients treated have responded to initial treatment, while many experience complete remission. However, a subset of patients do not respond to Gleevec therapy fully or at all, and ever year around four to five percent of successfully treated patients will develop resistance to Gleevec during therapy with a return of their disease manifestations.

The licencing agreement will result in one of several major new cancer diagnostic tests planned by Genzyme Genetics this year, all of which will be designed to help identify which patients are likely to respond to targeted cancer therapies. In July the company unveiled its first cancer test to complement treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL) with drugs such as Campath (alemtuzumab), and has recently launched a test to specifically identify epidermal growth factor receptor (EGFR) mutations associated with non-small cell lung cancer.

'This new test is designed to identify those patients who are likely to respond to Gleevec, as well as those who are likely to develop resistance to the drug,' said Mara Aspinall, president of Genzyme Genetics. 'Because CML is a chronic disease requiring ongoing therapy, the literature suggests that the long-term morbidity and quality of life should improve for many patients as a result of physicians having access to this test.'

CML, also known as chronic myelogenous leukemia, is, according to the American Cancer Society, 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. In contrast, other types of non-leukaemia cancer can start in these organs and then spread to the bone marrow (or elsewhere). CML can also change into a fast-growing acute leukaemia that invades almost any organ in the body. The American Cancer Society estimates that approximately 4,600 new cases of CML were diagnosed in the US in 2005, while around 25,000 CML patients are in remission on therapy in the US.