-   FLT3 mutation-positive AML is a life-threatening disease  
with significant unmet medical needs   -

-   XOSPATA is the first and only FLT3 inhibitor approved by the FDA 
for patients with relapsed or refractory AML with a FLT3 mutation   -

-   Approval of XOSPATA marks Astellas’ U.S. entry
 into the treatment of blood cancers   -

TOKYO – November 29, 2018 – Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D. “Astellas”) today announced that the U.S. Food and Drug Administration (FDA) approved XOSPATA® (generic name: gilteritinib) for the treatment of adult patients who have relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test.  XOSPATA is an oral therapy and the first and only FLT3-targeting therapy to be approved by the FDA for this population. 

The American Cancer Society estimates that in 2018, approximately 19,000 people will be diagnosed with AML in the U.S.  AML has been associated with various genetic mutations. XOSPATA has demonstrated inhibitory activity against two different mutations, FLT3 internal tandem duplication (ITD) and FLT3 tyrosine kinase domain (TKD).2 Impacting approximately 30 percent of AML patients,  the FLT3-ITD mutation is associated with worsened disease free survival and overall survival. ,  FLT3-TKD mutations impact approximately 7 percent of AML patients4 and, although the impact of these mutations is less clear,  they have been associated with treatment resistance.  

“Our ability to use precision medicine to help patients with FLT3-mutated AML takes an important step forward with the approval of XOSPATA,” said Alexander Perl, M.D., Abramson Cancer Center, University of Pennsylvania. “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." 

“XOSPATA offers new hope to patients for whom the treatment path forward is unclear,” said Steven Benner, M.D., senior vice president and global therapeutic area head, Oncology Development, Astellas. “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.”

The FDA’s approval of XOSPATA was based on an interim analysis of the following endpoints in the ADMIRAL clinical trial: the rate of complete remission (CR)/complete remission with partial hematologic recovery (CRh); the duration of CR/CRh (DOR); and the rate of conversion from transfusion dependence to transfusion independence. The CR/CRh rate was 21%. The median duration of CR/CRh was 4.6 months. The rate of conversion from transfusion dependence to transfusion independence was 31.1% for any 56 day post-baseline period. For patients who achieved a CR/CRh, the median time to first response was 3.6 months (range, 0.9 to 9.6 months). The CR/CRh rate was 29 of 126 in patients with FLT3-ITD or FLT3-ITD/TKD and 0 of 12 in patients with FLT3-TKD only.

Full results from the ADMIRAL trial will be submitted for presentation at an upcoming medical meeting. 

The safety evaluation of XOSPATA was based on 292 patients with relapsed or refractory AML treated with 120 mg gilteritinib daily. The median duration of exposure to XOSPATA was 3 months (range 0.1 to 42.8 months). The most frequent non-hematological serious adverse reactions (≥5%) reported in patients were pneumonia (19%), sepsis (13%), fever (13%), dyspnea (7%) and renal impairment (5%). Overall, 22 of 292 patients (8%) discontinued XOSPATA treatment permanently due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were pneumonia (2%), sepsis (2%) and dyspnea (1%). The most common adverse reactions (≥20%) were myalgia/arthralgia (42%), transaminase increased (41%), fatigue/malaise (40%), fever (35%), non-infectious diarrhea (34%), dyspnea (34%), edema (34%), rash (30%), pneumonia (30%), nausea (27%), stomatitis (26%), cough (25%), headache (21%), hypotension (21%), dizziness (20%) and vomiting (20%).

Previously, XOSPATA was granted both Orphan Drug designation  and Fast Track  designation by the U.S. FDA. Gilteritinib also received Orphan Designation from the European Commission (EC)  and Orphan Drug Designation from the Japan Ministry of Health, Labor and Welfare (MHLW).  The MHLW also granted SAKIGAKE designation to gilteritinib for FLT3mut+ relapsed/refractory AML and approved the treatment for this population in September 2018.  

Astellas reflected the impact from this approval in its financial forecast of the current fiscal year ending March 31, 2019.