FDA Approves Gleevec as First-Line Treatment of Patients With CML

ROCKVILLE, Maryland-The US Food and Drug Administration (FDA) has approved Gleevec (imatinib mesylate, Novartis) for the first-line treatment of patients with chronic myeloid leukemia (CML) (see January 2003 ONI, page 1). The agency initially approved the drug in May 2001 for treating the advanced stages of CML. Gleevec first received accelerated approval, which required the company to conduct phase IV postmar-keting research to show that the drug provided clinical benefit in advanced CML and to assess its effect in patients with early-stage disease. With its latest action, FDA has now approved Gleevec as therapy for all three stages of CML-blast crisis, accelerated, and chronic-either before or after other therapies.

Gleevec targets a blood-cell enzyme that is continuously expressed as the result of the genetic translocation in the nucleus that creates the Philadelphia chromosome. The free-flowing enzyme results in potentially fatal levels of mature and immature white blood cells in the bone marrow and blood. By inhibiting the enzyme, Gleevec blocks the growth of the white blood cells.

The recent FDA action was based on a clinical trial that enrolled and randomized 1,106 newly diagnosed CML patients. Half the patients received Gleevec and the other 553 received the standard CML therapy combination of interferon-alfa and cytarabine. After 1 year, the Gleevec group had significantly fewer cancerous cells in their blood and bone marrow than those receiving the standard treatment, and their rate of disease progression was decreased as well. The study’s 14-month follow-up was too short to measure any long-term benefits of Gleevec, such as improved survival.