Phase 3 ADMIRAL Trial Data Show XOSPATA® (gilteritinib) Significantly Prolongs Overall Survival in Adult Patients with FLT3 Mutation-Positive Relapsed/Refractory Acute Myeloid Leukemia Compared with Salvage Chemotherapy

TOKYO, April 1, 2019 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503) (President and CEO: Kenji Yasukawa, Ph.D. "Astellas") today announced results from the Phase 3 ADMIRAL clinical trial comparing XOSPATA^® (gilteritinib) to salvage chemotherapy in adult patients with relapsed or refractory (resistant to treatment) Acute Myeloid Leukemia (AML) with a FLT3 mutation. The results show that patients treated with XOSPATA had significantly longer Overall Survival (OS) than those who received standard salvage chemotherapy. The data were shared today by Alexander Perl, M.D., Abramson Cancer Center, University of Pennsylvania, in a press conference at the American Association for Cancer Research (AACR) Annual Meeting. The data will also be presented during the AACR Clinical Trials Plenary Session (#CT184), which takes place April 2, 2019, 10:30 a.m. – 12:45 p.m. at the Georgia World Congress Center, Marcus Auditorium, Bldg A-GWCC.

Results from the ADMIRAL trial show the median OS for patients who received XOSPATA was 9.3 months compared to 5.6 months for patients who received salvage chemotherapy (Hazard Ratio = 0.637 (95% CI 0.490, 0.830), P=0.007); one-year survival rates were 37% for patients who received XOSPATA compared to 17% for patients who received salvage chemotherapy.

The most common treatment-emergent adverse events (TEAEs) of any grade occurring in ≥10% of patients during the first 30 days of treatment with gilteritinib were anemia (33%), increased alanine aminotransferase (24%), increased aspartate aminotransferase (24%), febrile neutropenia (21%), thrombocytopenia (19%), constipation (17%), pyrexia (15%), fatigue (15%), decreased neutrophil count (14%), increased blood alkaline phosphatase (13%), nausea (13%), hypokalemia (11%), cough (11%), headache (10%), and diarrhea (10%). The most common TEAEs of any grade occurring in ≥10% of patients during the first 30 days of treatment with salvage chemotherapy were anemia (33%), febrile neutropenia (32%), nausea (30%), diarrhea (28%), hypokalemia (27%), pyrexia (26%), decreased appetite (17%), decreased white blood cell count (17%), thrombocytopenia (16%), constipation (14%), abdominal pain (14%), hyperglycemia (13%), headache (13%), stomatitis (13%), fatigue (11%), decreased neutrophil count (11%), increased aspartate aminotransferase (10%), vomiting (10%), peripheral edema (10%), and hypomagnesemia (10%).

"We are very encouraged by the findings of the ADMIRAL trial," said Alexander Perl, M.D., an associate professor of Hematology-Oncology in Penn's Perelman School of Medicine. "Patients with relapsed/refractory FLT3 mutation-positive AML generally have a poor prognosis and short survival. Until just recently, they had few treatment options. These findings change the treatment paradigm for this patient population."

XOSPATA was approved by the U.S. Food and Drug Administration (FDA) in November 2018 for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation as detected by an FDA-approved test.[1]

XOSPATA was discovered through a research collaboration with Kotobuki Pharmaceutical Co., Ltd., and Astellas has exclusive global rights to develop, manufacture and commercialize XOSPATA.

XOSPATA was approved by the Japan Ministry of Health, Labor and Welfare (MHLW) for relapsed or refractory AML with FLT3 mutations and launched as XOSPATA^® 40 mg Tablets in 2018.[2] In February 2019, a marketing authorization application (MAA) for the oral once-daily therapy XOSPATA for the treatment of adult patients who have relapsed or refractory AML with a FLT3 mutation was accepted by the European Medicines Agency for regulatory review.[3]

Astellas is currently investigating gilteritinib in various FLT3 mutation-positive AML patient populations through several Phase 3 trials. Visit http://www.clinicaltrials.gov to learn more about ongoing gilteritinib clinical trials.

About the ADMIRAL Trial[4] 

The Phase 3 ADMIRAL trial (NCT02421939) was an open-label, multicenter, randomized study of gilteritinib versus salvage chemotherapy in adult patients with FLT3 mutations who are refractory to or have relapsed after first-line AML therapy. The primary endpoint of the trial was Overall Survival (OS). The study enrolled 371 patients with relapsed or refractory AML and positive for FLT3 mutations present in bone marrow or whole blood. Subjects were randomized in a 2:1 ratio to receive gilteritinib (120 mg)[5] or salvage chemotherapy.

About XOSPATA^® (gilteritinib)

 XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory Acute Myeloid Leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.1

About Astellas

Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. For more information, please visit our website at https://www.astellas.com/en.

[1] XOSPATA [package insert]. Northbrook, IL: Astellas Pharma US, Inc. 
[2] Astellas Pharma Inc. Astellas Announces Approval in Japan for XOSPATA® 40 mg Tablets for the Treatment of FLT3mut+ Relapsed or Refractory AML (09-21-2018). https://www.astellas.com/en/news/14271. Accessed 03-14-2019. 
[3] Astellas Pharma Inc. Astellas Announces Acceptance of XOSPATATM (gilteritinib) for Regulatory Review by the European Medicines Agency (02-28-2019). https://www.astellas.com/us/news/14631.  Accessed 03-14-2019. 
[4] ClinicalTrials.gov. A study of ASP2215 versus salvage chemotherapy in patients with relapsed refractory acute myeloid leukemia (AML) with FMS-like tyrosine kinase (FLT3) mutation (02-01-2019). https://clinicaltrials.gov/ct2/show/NCT02421939. Accessed 02-05-2019. 
[5] Gorcea CM, Burthem J, Tholouli E. ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial. Future Oncol (Epub) 03-02-2018.

SOURCE Astellas Pharma Inc.