New drug can successfully treat patients who have become resistant to Gleevec

Dec 5 2004

A team of prominent researchers led by Charles Sawyers, M.D. and Moshe Talpaz, M.D., presented compelling clinical findings today showing that a new drug, BMS-354825, can successfully treat patients who have become resistant to Gleevec (the frontline therapy for chronic myelogenous leukemia, CML). Dr. Sawyers and Dr. Talpaz presented results of a phase I clinical trial at the annual meeting of the American Society of Hematology in San Diego.

The trial showed that 86 percent of the patients treated with BMS-354825 achieved a complete hematologic response (complete remission). A Specialized Center of Research (SCOR) grant from The Leukemia & Lymphoma Society financed the discovery of the major mechanism of resistance to Gleevec, and identified the compound that circumvents resistance.

"These results are extremely promising for CML patients who develop resistance to Gleevec," stated Alan Kinniburgh, Ph.D., Senior Vice President of Research for The Leukemia & Lymphoma Society. "The Society is extremely proud to have funded the research that led to the use of BMS 354825 in this trial."

Gleevec, approved by the FDA in 2001, has proven extremely successful in targeting cancer cells with minimal damage to normal ones by inhibiting the BCR-ABL protein that is the hallmark of CML. Some CML patients develop resistance to Gleevec and may relapse after several months.

Through research funded by the Society, Dr. Sawyers was able to identify the mechanism that caused patients to become resistant to Gleevec -- mutations in the BCR-ABL gene that interfere with the ability of the drug to block BCR-ABL kinase activity. The researchers have uncovered a Bristol-Myers Squibb compound that successfully stops the activity of the vast majority of mutations found in patients who were Gleevec-resistant.

"The identification of this compound as a drug candidate is a direct result of knowing why patients develop resistance to Gleevec," said Dr. Sawyers, of the UCLA Jonsson Cancer Center in Los Angeles, CA. "The data from this study provide compelling evidence supporting the safety and efficacy of BMS-354825."

In the trial, 31 of 36 patients had a complete hematologic response (complete remission). Of 29 patients evaluated for cytogenetic response, 13 had reductions in the number of Philadelphia chromosomes.

The Leukemia & Lymphoma Society also funded the research that led to the original use of Gleevec in treating CML. Brian Druker, M.D., Howard Hughes Medical Institute investigator and HELD-WEN Chair of Leukemia Research at the Oregon Health & Science University Cancer Institute, developed Gleevec as a treatment for CML with research funding from the Society.

In 2000, the Society awarded a $7.5 million Specialized Center of Research (SCOR) grant over a 5-year period, to Dr. Druker and his collaborators, including Dr. Sawyers, to expand on their earlier Specialized Center of Research grants. The cornerstone of the $77 million SCOR program, the Society's largest and most innovative research initiative, is its collaborative structure: every recipient works with leader researchers from other universities and medical institutions. The concept behind the program is that leukemia, lymphoma and myeloma treatments and cures will be discovered most quickly in an environment of collaboration and teamwork.