Bosutinib Heads Toward Conditional Approval for CML in Europe

The European Medicines Agency (EMA) adopted a “positive opinion” earlier this year regarding conditional marketing approval for bosutinib for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). The approval would be for patients with chronic phase, accelerated phase, or blast phase CML who were previously treated with at least one other tyrosine kinase inhibitor, and for whom other agents including imatinib, nilotinib, and dasatinib are not options.

Ball-and-stick model of bosutinib

“We believe that bosutinib, if approved by the European Commission, would represent an important option for patients with CML who have progressed on prior treatment and are not candidates for alternative treatments,” said Mace Rothenberg, MD, senior vice president of clinical development and medical affairs in the Pfizer Oncology Business Unit, in a press release. “We believe many doctors and CML patients will find this treatment, if approved, to be a welcome addition, offering a distinct adverse event profile and a convenient once-daily dosing regimen.”

Bosutinib works by inhibiting the ABL and SRC signaling pathways, and was approved in the United States in September 2012 for treatment of chronic, accelerated, or blast phase CML with resistance or intolerance to other therapies. The EMA positive opinion was based on results from an ongoing phase I/II study known as Study 200, which has enrolled 571 patients.

The first part of the study established a dose for bosutinib in CML patients, and the second part is testing the efficacy of 500 mg daily in both CML and acute lymphocytic leukemia patients. The EMA’s approval would be conditional, a status granted to “a medicinal product that fulfills an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required.”

Some of those additional data may still come from the ongoing randomized phase III BELA trial. Primary results from that study were published last year and showed that bosutinib was no better than imatinib for newly chronic phase CML patients, but long-term results will still shed light on duration of response and other outcomes. The BELA trial did show that serious adverse events were more common with bosutinib than imatinib.

The EMA’s decision, made by the Committee for Medicinal Products for Human Use, will be reviewed by the European Commission; Pfizer said in the press release they expect a decision on conditional approval for bosutinib within a few months.