FDA approves addition of survival data to gilteritinib label for refractory AML with a FLT3 mutation

On May 29, 2019, the Food and Drug Administration approved the addition of overall survival data in labeling for gilteritinib (XOSPATA, Astellas Pharma US, Inc.), indicated for adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.

Approval was based on the ADMIRAL trial (NCT02421939), which included 371 adult patients with relapsed or refractory AML having a FLT3 ITD, D835, or I836 mutation by the LeukoStrat® CDx FLT3 Mutation Assay. Patients were randomized (2:1) to receive XOSPATA 120 mg once daily (n=247) over continuous 28-day cycles or prespecified salvage chemotherapy (n=124). Salvage chemotherapy included either intensive cytotoxic chemotherapy or a low-intensity regimen.

For the analysis, overall survival (OS) was measured from the randomization date until death by any cause. The median OS was 9.3 months for patients receiving gilteritinib and 5.6 months for those on the chemotherapy arm (HR 0.64; 95% CI: 0.49,0.83; 1 sided p-value=0.0004). The results were consistent in the intensive chemotherapy stratum (HR 0.66; 95% CI: 0.47-0.93) and the low-intensity regimen stratum (HR 0.56; 95% CI: 0.38-0.84).

The adverse reactions occurring in at least 20% of patients receiving gilteritinib were increased transaminase, myalgia/arthralgia, fatigue/malaise, fever, mucositis, edema, rash, noninfectious diarrhea, dyspnea, nausea, cough, constipation, eye disorders, headache, dizziness, hypotension, vomiting, and renal impairment. Prescribing information contains a Boxed Warning alerting health care professionals and patients about the risk of differentiation syndrome, which may be life-threatening or fatal if not treated.

The recommended gilteritinib dose is 120 mg orally once daily.

View full prescribing information for XOSPATA.

This application used the Real-Time Oncology Review and Assessment Aid pilot programs. FDA granted this application priority review and fast track designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 Systemby calling 1-800-FDA-1088.

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