Bosutinib (Bosulif, Pfizer Inc.) is now FDA-approved to treat adults with newly diagnosed chronic-phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).
The FDA gave the supplemental new drug application to expand the indication for bosutinib priority review and granted accelerated approval based on molecular and cytogenetic response rates. Continued approval for this indication may depend on verification and confirmation of clinical benefit in an ongoing long-term follow-up trial.
The FDA first approved bosutinib in September 2012 for the treatment of adults with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.
“Among patients with CML today, with the various treatment options available, it is important to recognize the unique needs of each of my CML patients and prescribe treatments that best meet those needs,” said Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center. “The efficacy and distinct tolerability profile of Bosulif make it an important and useful treatment option for newly diagnosed CML patients.”
The approval was based on results from BFORE (Bosutinib trial in First line chrOnic myelogenous leukemia tREatment), a randomized multicenter, multinational, open-label phase 3 study that showed bosutinib 400 mg was associated with a significantly higher rate of patients achieving major molecular response (MMR) at 12 months (47.2%; 95% confidence interval [CI], 40.9–53.4) compared to the rate achieved in patients treated with imatinib (Gleevec, Novartis) 400 mg (36.9%; 95% CI, 30.8–43.0), a current standard of care (two-sided P = 0.0200).
Complete cytogenic response (CCyR) rate by 12 months was 77.2% (95% CI, 72.0–82.5) for patients treated with bosutinib compared with 66.4% (95% CI, 60.4–72.4) for patients treated with imatinib (two-sided P = 0.0075). The adverse events seen in the trial were consistent with the known safety profile for bosutinib. The most common adverse reactions in newly diagnosed CML patients treated with bosutinib (incidence greater than or equal to 20%) are diarrhea (70%), nausea (35%), thrombocytopenia (35%), rash (34%), increased alanine aminotransferase (31%), abdominal pain (25%), and increased aspartate aminotransferase (23%).
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.
CML is a rare blood cancer that begins in the bone marrow but often moves into the blood. Researchers estimate that by 2020, more than 412,000 people worldwide will be diagnosed with leukemia (all types). CML accounts for 10% to 15% of all incident leukemia cases. In the U.S., approximately 48,000 people are living with CML. Around 9,000 new CML cases were expected to be diagnosed in the U.S. in 2017.
Bosutinib) is an oral, once-daily, tyrosine kinase inhibitor (TKI) that inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases.
Source: Pfizer Inc.; December 19, 2017