Regulatory Decision Summary for Bosulif

From review of this submission, Bosulif (bosutinib) is recommended for the treatment of adult patients with newly-diagnosed Philadelphia-positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP) based on the safety and efficacy results of pivotal study AV001. Study AV001 was a randomized (1:1), active-controlled, open-label, pivotal Phase 3 trial that compared bosutinib 400 mg (n = 268) taken orally once daily to imatinib (n = 265) 400 mg taken orally once daily.

Study AV001 met its primary endpoint of major molecular response (MMR) at 12 months, demonstrating that bosutinib was superior to imatinib: 47.2% vs. 36.9%, respectively. Median duration of MMR was not reached at cut-off date for either group. The study also met its key secondary endpoint, complete cytogenic response (CCyR) at 12 months, with 77.2% of patients achieving this endpoint in the bosutinib arm compared to 66.4% in the imatinib arm.

The most common treatment-emergent adverse events experienced by subjects receiving bosutinib in study AV001 were diarrhea (70.1%), nausea (35.1%), alanine transaminase (ALT) increased (30.6%), thrombocytopenia (23.9%), and aspartate transaminase (AST) increased (22.8%). The safety profile is similar to the known profile in adult patients treated in the 2nd line CML setting. No new safety signals were identified in study AV001.

Based on the results from the pivotal study AV001, the benefit-risk profile of Bosulif in the newly-diagnosed CML-CP population is deemed to be favourable. In addition, a new 400mg tablet was proposed and, after review, the submission was considered to comply with the quality data requirements.