Astellas Breaks into U.S. Blood Cancer Market with Approval of Xospata for AML

_{Blood smear under microscopy showing acute myeloid leukemia (AML)}

The U.S. Food and Drug Administration (FDA) green-lit a new treatment for acute myeloid leukemia (AML) patients who have a rare and life-threatening disease mutation developed by Astellas Pharma, Inc. The approval marks the company’s U.S. entry into blood cancer treatment.

Under priority review, the FDA approved Xospata (gilteritinib) for adult relapsed or refractory (resistant to treatment) AML patients who have an FLT3 mutation as detected by an FDA-approved test. As of now, this is the first and only FLT3-targeting therapy to be approved by the FDA for this patient population. Of the 19,000 people in the United States who are estimated to be diagnosed with AML this year, nearly 40 percent will have an FLT3 mutation. The Astellas drug has shown itself to be effective against two FLT3 mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).

The first FLT3-targeted therapy for AML was FDA approved in April of 2017, Novartis' Rydapt (midostaurin). This medication is approved for patients with newly diagnosed AML who have an FLT3 mutation, as detected by an FDA-approved test, in combination with chemotherapy. 

The FLT3-ITD mutation is associated with worsened disease-free survival and overall survival and impacts about 30 percent of AML patients. In its announcement, Astellas said the FLT3-TKD mutations impact approximately 7 percent of AML patients. However, while the impact of these mutations is not as understood as the FLT3-ITD mutation, they have been associated with treatment resistance, the company said.

Steven Benner, global therapeutic area head in oncology for Japan-based Astellas, said Xospata provides new hope for AML patients who had an unclear path due to their mutation.

“For the first time, people with relapsed or refractory FLT3 mutation-positive AML have an FDA approved FLT3-targeting treatment available to them. The approval of XOSPATA is also a proud, landmark moment for our oncology program and marks the first approval of a medicine that will be the cornerstone of our new presence in blood cancers,” Benner said in a statement.

Alexander Perl of the Abramson Cancer Center at the University of Pennsylvania, touted the approval of Xospata as an “important step forward” in using precision medicine to help patient populations.

"There is an urgent need in the clinic for more targeted agents to help patients whose disease is either refractory to the initial therapy, or who have relapsed,” Perl added.

FDA approval for Xospata was based on an interim analysis of the Phase III ADMIRAL trial that included 138 adult AML patients with FLT3 mutations. After a median follow-up of 4.6 months, 29 patients achieved complete remission (CR) or CR with partial hematologic recovery, a 21 percent rate. For the 106 patients in the trial who were dependent on red blood cell and/or platelet transfusions at baseline, 31.1 percent (33 patients) became independent of transfusions. Also, the 32 patients in the study who did not require the transfusions, 53.1 percent remained transfusion-independent during any 56-day post-baseline period, the FDA said in its announcement. Xospata had been granted both Orphan Drug designation and Fast Track designation by the FDA.

The most common adverse reactions that occurred in less than 20 percent of trial patients included myalgia/arthralgia, transaminase increase, fatigue/malaise, fever, noninfectious diarrhea, dyspnea, edema, rash, pneumonia, nausea, stomatitis, cough, headache, hypotension, dizziness and vomiting, according to the FDA.

Astellas said full results of the ADMIRAL trial will be presented at an upcoming medical meeting.