ATLANTA—The FDA has granted accelerated approval to Bristol-Myers Squibb's Sprycel (dasatinib) Tablets 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 imatinib(Drug information on imatinib) (Gleevec). Sprycel also received regular FDA approval for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.

The approval came shortly after the FDA's Oncologic Drugs Advisory Committee (ODAC) signaled its support for the agent in a meeting held in Atlanta to coincide with ASCO's annual conference.

Dasatinib(Drug information on dasatinib) is an oral inhibitor of multiple tyrosine kinases, including BCR-ABL, SRC family, c-KIT, EPHA2, and PDGFRβ. It is promising because it is several hundred times more potent than imatinib at inhibiting the growth of cells harboring the BCR-ABL fusion gene and is effective in nearly all cells that have imatinib-resistant mutations, according to the sponsor.

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At the ODAC meeting, Claude Nicaise, MD, vice president, global development, Bristol-Myers Squibb, said, "We focused the development of dasatinib on the treatment of CML patients who failed imatinib because of
resistance or intolerance. These patients have limited therapeutic options, and dasatinib has the potential to fulfill this important unmet medical need."

Data on the drug come from six trials conducted at about 75 institutions worldwide in patients with all phases of CML who had imatinib resistance or intolerance and in patients with Ph+ ALL who had resistance or intolerance to prior therapy: a phase I dose-escalation trial, four single-arm phase II trials, and a randomized phase II trial pitting dasatinib against high-dose imatinib. (Data for the entire population in the randomized trial were presented at ASCO, see page 62.)

Efficacy analyses were based mainly on 529 patients enrolled in the phase I and single-arm phase II trials, which have a planned follow-up of 2 years. Most of these patients had CML in chronic phase (226 patients), accelerated phase (118), or myeloid blast phase (97); fewer had CML in lymphoid blast phase (47) or had Ph+ ALL (41). Only 94 patients (18%) overall had imatinib intolerance, and the majority of these were in the chronic phase CML group. Based on findings of the phase I trial, a dose of 70 mg twice daily was selected for use in the phase II trials, Dr. Nicaise said.

Efficacy results showed that among patients with chronic phase CML, 31% to 38% of imatinib-resistant patients and 73% to 75% of imatinib-intolerant patients had a major cytogenetic response, depending on the trial. Additionally, data from the first 36 patients enrolled in the randomized phase II trial, which was restricted to patients with chronic phase CML with imatinib resistance, showed a major cytogenetic response rate of 45% with dasatinib, compared with 21% with high-dose imatinib.