On October 17, 2018 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that it has submitted a New Drug Application (NDA) to Japan’s Ministry of Health, Labor and Welfare (MHLW) for marketing approval of quizartinib for the treatment of adult patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML) (Press release, Daiichi Sankyo, OCT 17, 2018, https://www.prnewswire.com/news-releases/daiichi-sankyo-submits-application-in-japan-for-flt3-inhibitor-quizartinib-for-treatment-of-patients-with-relapsedrefractory-flt3-itd-aml-300732661.html [SID1234529954]). The submission to Japan MHLW is based on the results of the pivotal randomized phase 3 QuANTUM-R study in the U.S., EU and Asia excluding Japan, and an open-label phase 2 study of quizartinib in Japan in patients with relapsed/refractory FLT3-ITD AML.
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"Quizartinib has been designed as a specific inhibitor of FLT3 with high affinity for FLT3-ITD, a driver mutation in AML that is linked to poor prognosis and is associated with aggressive disease that results in increased relapse rate and reduced overall survival for patients compared to those without this mutation," said Kouichi Akahane, PhD, MBA, Executive Officer, Head of Oncology Function, R&D Division, Daiichi Sankyo. "We look forward to working closely with the Japan Health Authority on our application for quizartinib in order to bring this important potential new targeted treatment option to patients with relapsed/refractory FLT3-ITD AML in Japan."
Quizartinib is the first FLT3 inhibitor to prolong overall survival as an oral, single agent compared to chemotherapy in patients with relapsed/refractory FLT3-ITD AML. This was demonstrated in a randomized phase 3 trial (QuANTUM-R) and topline results of QuANTUM-R were presented during the plenary program at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in June 2018.
The open-label, single arm phase 2 study evaluating quizartinib in Japanese patients with relapsed/refractory FLT3-ITD AML met its primary endpoint of achieving a predetermined composite complete remission rate at interim analysis, triggering an early stop of the study due to efficacy. The quizartinib efficacy and safety profile observed in the phase 2 study in Japan appears consistent with that of QuANTUM-R. These data were presented at the 80th Annual Meeting of the Japanese Society of Hematology (JSH) in October 2018.
In the QuANTUM-R study, the median treatment duration with quizartinib was 4 cyles of 28 days versus 1 cycle in the salvage chemotherapy arm. Incidence of treatment-emergent adverse events was comparable between patients who received single agent quizartinib and those who received salvage chemotherapy. The most common adverse events (>30 percent, any Grade) in patients treated with quizartinib included nausea, thrombocytopenia, fatigue, musculoskeletal pain, pyrexia, anemia, neutropenia, febrile neutropenia, vomiting and hypokalemia, and the most common Grade ≥ 3 adverse events (>20 percent) were thrombocytopenia, anemia, neutropenia and febrile neutropenia. The safety profile observed in QuANTUM-R appears consistent with that observed at similar doses in the quizartinib clinical development program.
About FLT3-ITD Acute Myeloid Leukemia
AML is an aggressive blood and bone marrow cancer that causes uncontrolled growth and accumulation of malignant white blood cells that fail to function normally and interfere with the production of normal blood cells.1 FLT3 gene mutations are one of the most common genetic abnormalities in AML.2 FLT3-ITD is the most common FLT3 mutation, affecting approximately one in four patients with AML.3,4,5,6 FLT3-ITD is a driver mutation that presents with high leukemic burden and has poor prognosis and a significant impact on disease management for patients with AML.4,7
Patients with FLT3-ITD AML have a worse overall prognosis, including an increased incidence of relapse, an increased risk of death following relapse and a higher likelihood of relapse following hematopoietic stem cell transplantation as compared to those without this mutation.8,9
About Quizartinib
Quizartinib, the lead investigational agent in the AML Franchise of the Daiichi Sankyo Cancer Enterprise, is an oral selective FLT3 inhibitor currently in phase 3 development for relapsed/refractory FLT3-ITD AML (QuANTUM-R) in the U.S. and EU; phase 3 development for newly-diagnosed FLT3-ITD AML (QuANTUM-First) in the U.S., EU and Japan; and, phase 2 development for relapsed/refractory FLT3-ITD AML in Japan.
Quizartinib has been granted Breakthrough Therapy designation for the treatment of adult patients with relapsed/refractory FLT3-ITD AML, and Fast Track designation for the treatment of relapsed/refractory AML by the U.S. Food and Drug Administration (FDA). Quizartinib also has been granted Orphan Drug designation by both the FDA and the European Commission (EC) for the treatment of AML and by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of FLT3-mutated AML.
Quizartinib is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.