Singapore, Jan 30, 2012: The US Food and Drug Administration (FDA) has accepted Pfizer's new drug application (NDA) for standard review of bosutinib as a treatment option for adult patients with previously treated Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML). This submission was based on efficacy and safety data from Study 200, a single-arm study of bosutinib in over 500 patients with previously treated Ph+ CML, including patients resistant or intolerant to imatinib as well as patients who were previously treated with dasatinib or nilotinib. Currently, there are no approved therapies available for CML patients after second-line treatment with dasatinib or nilotinib.
CML, one of the four main types of leukemia, accounts for 15 percent of all leukemias worldwide. Despite the availability of existing treatments, there remains a need for additional options for CML patients, given observed treatment–related toxicities and resistance.
“This filing underscores our commitment to bringing innovative treatment options to hematologic patient populations like CML, where the need for additional treatment options exists,” said Mr Garry Nicholson, president and general manager of the Pfizer Oncology Business Unit. “We are excited about the potential to bring this promising agent to those patients who fail or progress on previous therapies.”
Bosutinib is an oral, once-daily, investigational dual Src and Abl kinase inhibitor with minimal inhibitory activity against c-kit and PDGFR. It is believed that, by dual inhibition of the Src and Abl tyrosine kinases, bosutinib may inhibit signaling in CML cells that allows the cells to grow, survive and reproduce.4
A hallmark of CML is an abnormal chromosome known as the Philadelphia chromosome, a DNA mutation that initiates a series of events leading to the development of Bcr-Abl, a tyrosine kinase that causes CML cells to grow and reproduce rapidly.5 In some cases, resistance may develop to currently available therapies that inhibit Bcr-Abl.6 Inhibition of both Src and Abl tyrosine kinases may help overcome this resistance,7 as overexpression of the Src family of tyrosine kinases has been implicated in resistance and CML progression.