FDA Grants Accelerated Approval to Bosutinib

It is indicated in treatment of newly-diagnosed Ph-positive CML

On 19 December 2017, the US Food and Drug Administration (FDA) granted accelerated approval to bosutinib (BOSULIF, Pfizer Inc.) for treatment of patients with newly-diagnosed chronic phase (CP) Philadelphia chromosome (Ph)-positive chronic myelogenous leukaemia (CML).

Approval was based on data from an open-label, randomised, multicentre trial (BFORE, NCT02130557) in 487 patients with Ph-positive newly-diagnosed CP CML who were randomised to receive either bosutinib 400 mg once daily or imatinib 400 mg once daily. The major efficacy outcome measure was major molecular response (MMR) at 12 months, defined as ≤0.1% BCR ABL ratio on international scale (corresponding 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% (95% CI: 40.9, 53.4) in the bosutinib arm and 36.9% (95% CI: 30.8, 43.0) in the imatinib arm (p = 0.0200).

Most common adverse reactions in patients with newly-diagnosed CML (incidence ≥20%) are diarrhoea, nausea, thrombocytopenia, rash, increased alanine aminotransferase, abdominal pain, and increased aspartate aminotransferase.

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

The recommended dose of bosutinib for newly-diagnosed chronic phase Ph-positive CML is 400 mg orally once daily with food.

Full prescribing information is available here

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.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.