FDA Grants Accelerated Approval to Bosulif for Treatment of Newly-Diagnosed Chronic Myelogenous Leukemia

CancerConnect News: On December 19, 2017, the Food and Drug Administration granted accelerated approval to bosutinib Bosulif (bosutinib) for treatment of patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML).


Chronic myelogenous leukemia (CML) is a rare blood cancer, which begins in the bone marrow, but often moves into the blood.1 Researchers estimate that by 2020, more than 412,000 people worldwide will be diagnosed with leukemia (all types).2 CML accounts for 10-15% of all incident leukemia cases.1,3 In the U.S., approximately 48,000 people are living with CML.4 Around 9,000 new CML cases were diagnosed in the U.S. in 2017.1

Approval was based on data from an open-label, randomized, multicenter clinical trial performed in 487 patients with Ph+ newly-diagnosed CP CML who were treated with either Bosulif 400 mg once daily or Gleeved (imatinib) 400 mg once daily. The major efficacy outcome measure was major molecular response (MMR) at 12 months, defined as less than or equal to 0.1% BCR ABL ratio on international scale (corresponding to greater than or equal to 3 log reduction from standardized baseline) with a minimum of 3000 ABL transcripts as assessed by the central laboratory. MMR at 12 months was 47.2% in the bosulif group compared to 36.9% in the Gleevec treated patients.

Recognition of the pivotal role of the BCR-ABL protein in CML led to the development of Gleevec, which blocks the activity of this protein. Gleevec produced high rates of remission among patients with chronic-phase CML and dramatically changed the treatment of this disease. Newer drugs that target the BCR-ABL protein include Tasigna® (nilotinib) and Sprycel® (dasatinib). Both Tasigna and Sprycel appear to be superior to Gleevec for the initial treatment of patients with CML and are approved by the FDA for this purpose.

Bosulif is a third-generation tyrosine kinase inhibitor that targets both Abl and Src kinases. Targeting of Src by Bosulif is thought to be important, as over-expression of Src kinases has been associated with resistance to Gleevec.

FDA first approved bosulif in 2012 for treatment of patients with chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

FDA granted priority review and Orphan Drug designation to bosutinib for this application. As a condition of accelerated approval, further follow-up of patients in the BFORE trial is required. A description of FDA expedited programs is in the Guidance for Industry:


1 American Cancer Society. What is Chronic Myeloid Leukemia? http://www.cancer.org/acs/groups/cid/documents/webcontent/003112-pdf.pdf. Accessed August 2017.

2 GLOBOCAN Online Analysis/Prediction. http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World…. Accessed December 2017.

3 Hochhaus, A. Educational Session: Managing Chronic Myeloid Leukemia as a Chronic Disease. American Society of Hematology. 2011; 10: 1.

4 National Cancer Institute. Surveillance Epidemiology and End Results (SEER) Cancer Stat Facts: Chronic Myeloid Leukemia (CML). https://seer.cancer.gov/statfacts/html/cmyl.html. Accessed December 2017.

Copyright © 2018 CancerConnect. All Rights Reserved.