FDA approved a supplemental New Drug Application to expand the indication for Bosulif (bosutinib) to include adult patients with newly-diagnosed chronic phase Philadelphiachromosome-positive chronic myelogenous leukemia.
The sNDA was reviewed and approved under the FDA’s Priority Review and accelerated approval programs based on molecular and cytogenetic response rates. Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow up trial.
Bosulif, sponsored by Pfizer, was first approved in September 2012 in the U.S. for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy.
The approval was based on results from BFORE (Bosutinib trial in first line chronic myelogenous leukemia treatment), a randomized multicenter, multinational, open-label phase III study which showed Bosulif 400 mg was associated with a significantly higher rate of patients achieving major molecular response at 12 months (47.2%; 95% CI, 40.9-53.4) compared to the rate achieved in patients treated with imatinib 400 mg (36.9%; 95% CI, 30.8-43.0), a current standard of care (two-sided P=0.0200).
Complete cytogenic response rate by 12 months was 77.2% (95% CI: 72.0, 82.5) for patients treated with Bosulif compared to 66.4% (95% CI: 60.4, 72.4) for patients treated with imatinib (two-sided P=0.0075).
Pfizer and Avillion entered into an exclusive collaborative development agreement in 2014 to conduct the BFORE trial. Under the terms of the agreement, Avillion provided funding and conducted the trial to generate the clinical data used to support this application and other potential regulatory filings for marketing authorization for Bosulif as first-line treatment for patients with chronic phase Ph+ CML. With this approval, Avillion is eligible to receive milestone payments from Pfizer. Pfizer retains all rights to commercialize Bosulif globally.
Bosulif (bosutinib) is an oral, once-daily, tyrosine kinase inhibitor, which inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases.
In the U.S., Bosulif (bosutinib) is now indicated for the treatment of patients with newly-diagnosed chronic phase Philadelphiachromosome-positive chronic myelogenous leukemia and for the treatment of adult patients with chronic, accelerated or blast phase Ph+ CML with resistance or intolerance to prior therapy (first approved in September 2012).
A 400 mg tablet was also recently approved by the FDA in addition to the previously approved 100 mg and 500 mg strengths. The recommended dose for newly-diagnosed patients is 400 mg orally once daily with food. For patients who are resistant or intolerant to prior tyrosine kinase inhibitor therapy, the recommended dose is 500 mg orally once daily with food.
In Europe, Bosulif was granted conditional marketing authorization in March 2013 for the treatment of adult patients with Ph+ CML previously treated with one or more TKIs and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options. The European Medicines Agency (EMA) has also validated for review a Type II Variation application for use of Bosulif in the same patient population.
BFORE is a randomized, multicenter, open-label phase III study designed to assess the effectiveness and safety of Bosulif (bosutinib) as a first-line treatment for patients with chronic phase Ph+ CML.
The study enrolled 536 patients at multiple sites in North America, Asia and Europe. Patients were randomized 1:1 to receive Bosulif 400 mg or imatinib 400 mg, a standard of care, for the duration of the study.
The primary outcome was to show superiority of Bosulif over imatinib at 12 months by comparing MMR, or the proportion of patients in each arm whose levels of the Bcr-Abl1 kinase have dropped below 0.1%.
