FDA Approves Gilteritinib for Relapsed or Refractory AML With a FLT3 Mutation

Approval is based on an interim analysis of the ADMIRAL trial

On 28 November 2018, the US Food and Drug Administration (FDA) approved gilteritinib (XOSPATA, Astellas Pharma US Inc.) for treatment of adult patients who have relapsed or refractory acute myeloid leukaemia (AML) with a FLT3 mutation as detected by an FDA-approved test. 

The FDA also approved an expanded indication for a companion diagnostic, to include use with gilteritinib. The LeukoStrat CDx FLT3 Mutation Assay, developed by Invivoscribe Technologies, Inc., is used to detect the FLT3 mutation in patients with AML. 

Approval of gilteritinib was based on an interim analysis of the ADMIRAL trial (NCT02421939), which included 138 adult patients with relapsed or refractory AML having a FLT3 ITD, D835, or I836 mutation as detected by the LeukoStrat CDx FLT3 Mutation Assay. 

Gilteritinib was given orally at a dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit. After a median follow-up of 4.6 months (range 2.8 to 15.8), 29 patients achieved complete remission (CR) or CR with partial haematologic recovery (CRh) (21%, 95% CI: 14.5, 28.8). 

Among the 106 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, 33 (31.1%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. For the 32 patients who were independent of both RBC and platelet transfusions at baseline, 17 (53.1%) remained transfusion-independent during any 56-day post-baseline period. 

The most common adverse reactions occurring in ≥ 20% of patients were myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, non-infectious diarrhoea, dyspnoea, oedema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness and vomiting. 

The recommended gilteritinib dose is 120 mg orally once daily. 

Full prescribing information for XOSPATA is available here.

FDA granted this application fast track and priority review, as well as orphan product designation. 

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.