On October 25, 2019 Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") reported that the European Commission (EC) has approved the oral once-daily therapy XOSPATA (gilteritinib) as a monotherapy for the treatment of adult patients with relapsed or refractory (resistant to treatment) acute myeloid leukemia (AML) with a FLT3 mutation (FLT3mut+) (Press release, Astellas, OCT 25, 2019, View Source [SID1234542517]). Gilteritinib has the potential to improve treatment outcomes for AML patients with two forms of the most common mutation—FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD) mutation.1,2

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This approval is based on results from the Phase 3 ADMIRAL trial, which investigated gilteritinib versus salvage chemotherapy in patients with relapsed or refractory FLT3mut+ AML. Patients treated with gilteritinib had significantly longer overall survival (OS) than those who received salvage chemotherapy. Median OS for patients who received gilteritinib was 9.3 months, compared to 5.6 months for patients who received salvage chemotherapy (Hazard Ratio = 0.64 (95% CI 0.49, 0.83), P=0.0004). Rates of one-year survival were 37% for patients who received gilteritinib, compared to 17% for patients who received salvage chemotherapy.3,4

"AML is a rare cancer and patients with a FLT3 mutation have a particularly poor prognosis, with a median survival of less than six months following treatment with salvage chemotherapy," said Giovanni Martinelli, M.D., Institute of Hematology, S.Orsola-Malpighi University Hospital, Bologna, Italy, an investigator in the ADMIRAL trial. "Gilteritinib is a new and clinically meaningful treatment option that provides a welcome advance for patients and health care professionals across the European Union."

The EC marketing authorization for gilteritinib in relapsed or refractory FLT3mut+ AML is applicable to the European Union (EU) member countries, and is also valid in Iceland, Norway and Liechtenstein. Gilteritinib has been designated an orphan medicinal product and also received accelerated assessment from the European Medicines Agency earlier this year, which reduced the timeframe for approval.5,6,7

"Today’s approval marks a significant advance for patients living with relapsed or refractory, FLT3 mutation-positive acute myeloid leukemia," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Global Therapeutic Area Head, Oncology Development, Astellas. "We look forward to working with health authorities across the EU to bring gilteritinib to patients who need it the most, as soon as possible."

Patients’ FLT3mut+ status can change over the course of AML treatment, even after relapse. Due to the poor outcomes associated with FLT3mut+ AML, patients’ FLT3 mutation status may be confirmed to help inform the best treatment approach.8,9,10

Astellas reflected the impact from this approval in its financial forecast of the current fiscal year ending March 31, 2020.

About XOSPATA (gilteritinib)
Gilteritinib was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and commercialize gilteritinib. Gilteritinib was approved in the U.S. and Japan in 2018 for the treatment of adult patients who have relapsed or refractory FLT3mut+ AML.11,12

Astellas is currently investigating gilteritinib in various FLT3 mutation-positive AML patient populations through several clinical trials. Visit View Source to learn more about ongoing gilteritinib clinical trials.

About the ADMIRAL Trial
The Phase 3 ADMIRAL trial (NCT02421939) was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3mut+ who are refractory to or have relapsed after first-line AML therapy. The co-primary endpoints of the trial were OS and CR/CRh rates; OS, the primary endpoint at the trial’s final analysis, was the basis of EC approval. The study enrolled 371 patients with relapsed or refractory AML and FLT3mut+ present in bone marrow or whole blood. Subjects were randomized in a 2:1 ratio to receive gilteritinib (120 mg) or salvage chemotherapy.13

The most common adverse events (AEs) across both treatment arms of the ADMIRAL trial were febrile neutropenia (43.7%), anemia (43.4%), and pyrexia (38.6%). Common grade ≥3 AEs related to gilteritinib were anemia (19.5%), febrile neutropenia (15.4%), thrombocytopenia (12.2%), and decreased platelet count (12.2%). Adjusted for exposure duration, serious treatment-emergent AEs per patient year were less common with gilteritinib (7.1%) than salvage chemotherapy (9.2%).3