Glivec: A New Treatment Modality for CML: A Case History

Abstract

Glivec (the brand name in the US is Gleevec™) is a protein-tyrosine kinase inhibitor which potently inhibits the AbI tyrosine kinase in vitro and in vivo. The compound specifically inhibits proliferation of v-abl and bcr-abl expressing cells, suggesting that it is not a general antimitotic agent. In addition, Glivec is a potent inhibitor of the platelet-derived growth factor receptor kinase (PDGF-R) and of the receptor kinase for stem cell factor (SCF), c-Kit, and inhibits PDGF- and SCF-mediated biochemical events. In contrast, it does not affect signal transduction mediated by other stimuli including epidermal growth factor (EGF), insulin and phorbol esters. Pharmacokinetic studies in various animal species demonstrate that pharmacologically relevant concentrations are achieved in the plasma following oral administration of the drug. STI571 shows antitumor activity as a single agent in animal models at well-tolerated doses. On May 10, 2001, the U.S. Food and Drug administration announced the fast track approval of Gleevec™ (imatinib mesylate), our treatment for patients with chronic myeloid leukemia (CML) in blast crisis, accelerated phase or chronic phase after failure of interferon-alpha therapy. The FDA approval came in just over 10 weeks after Novartis filed its New Drug Application, and just two months after the FDA notified us that it had granted Glivec a priority review.