FDA Approves Gilteritinib for the Treatment of Adult Relapsed or Refractory AML with FLT3 Mutation

The US Food and Drug Administration (FDA) has approved Astellas Pharma’s gilteritinib (XOSPATA) for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.

A companion diagnostic that is to include use with gilteritinib is an expanded indication that has also been approved by the FDA. Developed by Invivoscribe Technologies, Inc., the LeukoStrat CDx FLT3 Mutation Assay detects the FLT3 mutation in patients with AML.

In an exclusive interview with Rare Disease Report^® at the 2018 ASCO Meeting, Steven Benner, MD, MHS, senior vice president and global therapeutic area head of Oncology, highlighted the primary challenges of treating AML as well as the treatment benefits gilteritinib provides. “Patients with AML have been found to have a series of different mutations that are important for driving the disease. One of the most common is the FLT3 mutation which occurs in about 30% of AML patients. When it occurs, it means those patients have more aggressive disease they are more likely to relapse and when they relapse, unfortunately, they do very poorly.”

“Consequently, our therapy is an oral therapy, which will allow us to target that specific mutation and it targets both the most common form—which is an internal tandem duplication of the mutation—but also a terminal mutation, which is what is associated with resistance to therapy. Our drug targets both of those types of FLT3 mutations. Since it’s a potent inhibitor, it has also been able to induce complete remissions, including deep molecular responses in patients that have received it as a single agent.”

Interim analysis of the ADMIRAL trial (NCT02421939) served as the basis for the approval. One hundred and thirty-eight adult patients with relapsed or refractory AML having a FLT3 ITD, D835, or I836 mutation by the LeukoStrat CDx FLT3 Mutation Assay were included in the trial.

At a dose of 120 mg daily until unacceptable toxicity or lack of clinical benefit, gilteritinib was administered orally. Twenty-nine patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh) (21%, 95% CI: 14.5, 28.8) following a median follow-up of 4.6 months (range: 2.8 to 15.8).

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

Myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness, and vomiting included the most common adverse reactions, which occurred in ≥ 20% of patients.

Gilteritinib dosing is recommended at 120 mg orally once daily.

Previously, the FDA granted gilteritinib fast track, priority review, and orphan drug designations.