U.S. FDA approves Sprycel (dasatinib) with two indications

07-26-2006

Bristol-Myers Squibb Company (BMY) announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Sprycel, an oral inhibitor of multiple tyrosine kinases, for the treatment of adults in all phases of chronic myeloid leukemia (CML) (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy, including Gleevec (imatinib mesylate).

The effectiveness of Sprycel is based on hematologic and cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival. The FDA also granted full approval of Sprycel for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy. Bristol-Myers Squibb anticipates that Sprycel will be available within days nationwide.

Sprycel is the first approved oral tyrosine kinase inhibitor predicted to bind to multiple conformations of the ABL kinase based on modeling studies. At nanomolar concentrations, dasatinib inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFR-B. By targeting these kinases, dasatinib inhibits the overproduction of leukemia cells in the bone marrow of patients with CML and Ph+ALL and allows normal red cell, white cell, and blood platelet production to resume.

"Sprycel provides a new treatment option for patients with CML or Ph+ALL who are resistant or intolerant to prior therapy," said Brian J. Druker, MD, investigator, Howard Hughes Medical Institute and JELD-WEN chair of Leukemia Research, Oregon Health & Science University Cancer Institute, Portland, Oregon.

Known mechanisms of imatinib resistance include mutations in the protein sequence of the BCR-ABL tyrosine kinase, multi-drug resistance gene overexpression, and the activation of alternate signaling pathways involving the SRC family kinases. For many patients with CML, the risk of developing resistance increases with the number of years of prior treatment and severity of disease. Patients with advanced Ph+ALL generally develop resistance more rapidly than CML patients, including those in blast phase (an average of 2 months versus 10 months, respectively).

"Sprycel builds on our company's long legacy of providing innovative oncology medicines to patients around the world," said Peter R. Dolan, chief executive officer, Bristol-Myers Squibb. "Discovered and developed in our own research facilities, Sprycel is a key part of our robust pipeline of anti-cancer compounds that holds the promise of further inroads in the struggle against this terrible disease. Our commitment to finding innovative medicines for patients is an important way that Bristol-Myers Squibb continues to live its mission."

The FDA reviewed the efficacy (n=445) and safety (n=911) of Sprycel based on the analysis of four Phase II multi-center studies in patients with resistance or intolerance to imatinib in all phases of CML (n=409) or Ph+ ALL (n=36). The studies were conducted on five continents (33 countries).

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2006, Biotech Business Week via NewsRx.com.