New Compound Overcomes Resistance to Gleevec

Main Category: Lymphoma / Leukemia / Myeloma
Article Date: 08 Dec 2004 - 11:00 PDT

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A team of prominent researchers led by Charles Sawyers, MD, and Moshe Talpaz, MD, 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).

Drs. Sawyers and Talpaz presented results of the successful Phase I clinical trial at the annual meeting of the American Society of Hematology (ASH) in San Diego, CA. Their work was financed by a Society Specialized Center of Research (SCOR) grant, which enabled them to discover the major mechanism of resistance to Gleevec and identify the compound that circumvents resistance.

The trial showed that 86 percent of the patients treated with BMS-354825, manufactured by Bristol-Myers Squibb, achieved a complete hematologic response (complete remission).

"These results are extremely promising for CML patients who develop resistance to Gleevec," said Alan Kinniburgh, Ph.D., senior vice president, Research Administration, 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, pioneered by Brian Druker, M.D., leader of the SCOR, was approved by the U.S. Food and Drug Administration in 2001 and has proven extremely successful in targeting cancer cells with minimal damage to normal ones. The drug inhibits the BCR-ABL protein, the hallmark of CML. But some CML patients develop resistance to Gleevec and may relapse after several months.

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. In addition, the researchers uncovered BMS-354825, the 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.

Innovative Society Research Program

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.

Dr. Druker and his collaborators, including Dr. Sawyers, were awarded a $7.5 million, five-year SCOR in 2000 to expand on earlier Society funding. Dr. Druker is the JELD-WEN Chair of Leukemia Research, Oregon Health & Science University Cancer Institute, and a Howard Hughes Medical Institute investigator.

About The Leukemia & Lymphoma Society

The Society, headquartered in White Plains, NY, with 63 chapters in the United States and additional branches in Canada, is the world's largest voluntary health organization dedicated to funding blood cancer research and providing education and patient services. The Society's mission: Cure leukemia, lymphoma, Hodgkin's disease and myeloma, and improve the quality of life of patients and their families. Since its founding in 1949, the Society has invested more than $360 million in research specifically targeting leukemia, lymphoma and myeloma. Last year alone, the Society made more than 812,000 contacts with patients, caregivers and healthcare professionals.

For more information about blood cancer, visit http://www.LLS.org or call the Society's Information Resource Center (IRC), a call center staffed by master's level social workers, nurses and health educators who provide information, support and resources to patients and their families and caregivers. IRC information specialists are available at (800) 955-4572, Monday through Friday, 9 a.m. to 6 p.m. ET.

http://www.leukemia-lymphoma.org
Contact: Andrea Greif, (914) 821-8958

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