Higher rates of molecular responses vs imatinib ¹

IN NEWLY DIAGNOSED ADULT PATIENTS WITH CP Ph + CML ¹

INDICATIONS BOSULIF ® ( bosutinib ) is indicated for the treatment of adult patients with :

• Newly diagnosed chronic phase ( CP ) Ph + chronic myelogenous leukemia ( CML )

• Chronic , accelerated , or blast phase Ph + CML with resistance or intolerance to prior therapy

MMR at 12 months PRIMARY ENDPOINT ¹

MMR by 5 years ¹

( 95 % CI , 41-53 ) n = 246

( 95 % CI , 69-80 ) n = 246

P = 0.0200 * OR = 1.52 ( 95 % CI , 1.02-2.25 )

* Derived from Cochran – Mantel – Haenszel test stratified by geographical region and Sokal risk score at randomization ; P value is 2-sided .

Deep molecular responses with BOSULIF by 5 years ²

Data below depict exploratory analyses that were not powered to detect statistical significance . No conclusion of efficacy can be drawn from these data . Lack of multiplicity adjustments can be a limitation of these analyses . ²

MR ⁴ by 5 years ² MR ^{4 . 5} by 5 years ²

( 95 % CI , 52.8-65.1 ) n = 246

( 95 % CI , 42.1-54.6 ) n = 246

Study design : BFORE is a randomized , 2-arm , open-label , multicenter trial in adult patients with newly diagnosed CP Ph + CML . Patients received 400 mg / day of BOSULIF or 400 mg / day of imatinib . Efficacy was assessed in the modified intent-to-treat ( mITT ) population , which included 487 patients with Ph + CML with typical BCR-ABL transcripts ( b2a2 and / or b3a2 ) at baseline and baseline BCR-ABL copies > 0 .

IMPORTANT SAFETY INFORMATION

Contraindications : History of hypersensitivity to BOSULIF . Reactions have included anaphylaxis .

Gastrointestinal Toxicity : Diarrhea , nausea , vomiting , and abdominal pain occur with BOSULIF . In the study of patients with newly diagnosed CP Ph + CML , the median time to onset for diarrhea ( all grades ) was 4 days and the median duration per event was 3 days . In the study of patients with CML who were resistant or intolerant to prior therapy , median time to onset of diarrhea ( all grades ) was 2 days , median duration was 2 days , and the median number of episodes per patient was 3 ( range 1-268 ). Monitor and manage patients using standards of care , including antidiarrheals , antiemetics , and / or fluid replacement . Withhold , dose reduce , or discontinue BOSULIF as necessary .

Myelosuppression : Thrombocytopenia , anemia , and neutropenia occur with BOSULIF . Perform complete blood counts weekly for the first month and then monthly thereafter , or as clinically indicated . Withhold , dose reduce , or discontinue BOSULIF as necessary .

Hepatic Toxicity : BOSULIF may cause elevations in serum transaminases ( alanine aminotransferase [ ALT ] and aspartate aminotransferase [ AST ]). Out of 1711 patients in BOSULIF clinical trials , 2 cases consistent with drug-induced liver injury have occurred without alternative causes . In the study of patients with newly diagnosed CP Ph + CML , the incidence of ALT and AST elevations was 68 % and 56 %, respectively . In patients with CML who were resistant or intolerant to prior therapy , the incidence of ALT and AST elevations was 53 % and 47 %, respectively ; sixty percent

of these patients experienced an increase in either ALT or AST . Perform hepatic enzyme tests at least monthly for the first 3 months and as clinically indicated . In patients with transaminase elevations , monitor liver enzymes more frequently . Withhold , dose reduce , or discontinue BOSULIF as necessary . In patients with mild , moderate , or severe hepatic impairment , the recommended starting dose is 200 mg daily .

Cardiovascular Toxicity : BOSULIF can cause cardiovascular toxicity , including cardiac failure , left ventricular dysfunction , and cardiac ischemic events . Cardiac failure events occurred more frequently in previously treated patients than in patients with newly diagnosed CML and were more frequent in patients with advanced age or risk factors , including previous medical history of cardiac failure . Cardiac ischemic events occurred in both previously treated patients and in patients with newly diagnosed CML and were more common in patients with coronary artery disease risk factors , including history of diabetes , body mass index greater than 30 , hypertension , and vascular disorders . In a randomized study of patients with newly diagnosed CML , cardiac failure occurred in 1.9 % of patients treated with BOSULIF compared to 0.8 % of patients treated with imatinib . Cardiac ischemic events occurred in 4.9 % of patients treated with BOSULIF compared to 0.8 % of patients treated with imatinib . In a single-arm study of patients with CML who were resistant or intolerant to prior therapy , cardiac failure was observed in 5.3 % of patients and cardiac ischemic events were observed in 4.9 % of patients treated with BOSULIF . Monitor patients for signs and symptoms consistent with cardiac failure and cardiac ischemia and treat as clinically indicated . Interrupt , dose reduce , or discontinue BOSULIF as necessary .

Please see the Brief Summary of Prescribing Information on the following pages .