The US Food and Drug Administration (FDA) has approved Pfizer Inc's Bosulif (bosutinib), an Abl and Src kinase inhibitor, for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukaemia (CML) with resistance, or intolerance to prior therapy. Patients in the registrational trial included patients who were previously treated with imatinib [Gleevec] or imatinib plus at least one second generation tyrosine kinase inhibitor (TKI).

Once daily Bosulif represents the only therapy approved with pivotal trial data that included CML patients treated with imatinib followed by a second generation TKI.

“Bosulif is the third new medicine from Pfizer Oncology’s pipeline to be approved by the FDA in just 13 months, a remarkable achievement that reflects our commitment to advancing the science in cancer drug development and delivering on Pfizer’s innovative core,” said Garry Nicholson, president and general manager, Pfizer Oncology Business Unit. “By focusing our pipeline on those compounds best positioned for advancement, we have been able to bring yet another important therapy to patients who urgently need it.”

Chronic myelogenous leukaemia is one of the four most common types of leukaemia, with more than 5,000 new cases diagnosed per year in the United States. Today, as many as 26,000 Americans are living with CML, a number that is expected to increase tenfold by 2040. While strides have been made in recent years, approximately one-third of patients receiving imatinib as initial therapy do not achieve an optimal response, and of those who ultimately require second generation TKIs, approximately half do not have a good outcome.

“Bosulif is an important new addition to the CML treatment landscape,” said Dr. Jorge E. Cortes, deputy chair and professor of medicine in the Department of Leukaemia at The University of Texas MD Anderson Cancer Center, and a lead investigator of the Pfizer-sponsored registrational study. “Despite recent advances, an unmet need remains for many CML patients who are refractory to one or more tyrosine kinase inhibitors.”

“As the first therapy in our growing haematology portfolio to receive approval by the FDA, Bosulif exemplifies Pfizer’s commitment to bringing meaningful new medicines to patients with haematologic cancers,” said Mace Rothenberg, vice president of Clinical Development and Medical Affairs, Pfizer Oncology Business Unit. “We believe many doctors and CML patients will find this treatment to be a welcome addition, offering a distinct adverse event profile and a convenient once-daily dosing regimen.”

Bosulif is a kinase inhibitor that limits cancer cell growth by inhibiting the Abl and Src signalling pathways. The recommended dose of Bosulif is 500 mg, orally, taken once daily, with food.

Study 200 is a global, single-arm, open-label, multi-cohort, phase 1/2 study of more than 500 patients with imatinib-resistant or –intolerant Ph+ CML with separate cohorts for chronic, accelerated and blast phase disease previously treated with one prior TKI (imatinib) or more than one TKI (imatinib followed by dasatinib and/or nilotinib).



The major cytogenetic response (MCyR) at 24 weeks for patients with chronic phase CML who had been previously treated with imatinib only (n=266) was 33.8 percent (95% CI: 28.2, 39.9). With a minimum follow-up of 23 months, 53.4 percent of patients achieved a MCyR. Of patients who achieved MCyR, 52.8 per cent had a MCyR lasting at least 18 months. The median duration of MCyR was not reached for these patients.

The MCyR by 24 weeks for patients with chronic phase CML who had been treated with imatinib and at least one other TKI (n=108) was 26.9 per cent (95% CI: 18.8, 36.2). With a minimum follow-up of 13 months, 32.4 percent of patients achieved a MCyR. Of patients who achieved MCyR, 51.4 per cent had a MCyR lasting at least nine months. The median duration of MCyR was not reached for these patients.

A low rate of transformation (4 per cent, n=16) from the chronic phase to the advanced or blast phase was also observed in patients treated with Bosulif.

The most common all grade adverse reactions (ARs) observed in the chronic phase of Study 200 included diarrhoea (84 per cent), nausea (46 per cent), abdominal pain (40 per cent), thrombocytopenia (40 per cent) and vomiting (37 per cent). Grade 3/4 ARs included thrombocytopenia (26 per cent), neutropenia (11 per cent), diarrhoea (9 per cent), anaemia (9 per cent) and rash (8 per cent).