On October 24, the Japanese pharmaceutical company Daiichi Sankyo announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for quizartinib and granted priority review: combining quizartinib with standard arabinoside Cytidine + anthracycline induction and standard cytarabine consolidation chemotherapy, and quizartinib as continuous monotherapy after consolidation, for the treatment of adult patients with newly diagnosed FLT3-ITD-positive acute myeloid leukemia (AML).
The FDA has set a target date for the Prescription Drug Filer Fee Act (PDUFA) of April 24, 2023. In March 2022, the FDA granted Fast Track designation (FTD) to quizartinib for the treatment of newly diagnosed FLT3-ITD-positive AML. In the European Union, Japan, and the United States, quizartinib has been granted Orphan Drug Designation (ODD) for the treatment of AML.
AML is one of the most common types of leukemia in adults, accounting for 23.1% of global leukemia cases in 2017. In the United States, there will be an estimated 20,050 new cases of AML in 2022, with a five-year survival rate of 30.5%. FLT3 (FMS-like tyrosine kinase 3) gene mutation is one of the most common genetic abnormalities in AML, of which FLT3-ITD (internal tandem duplication) is the most common type of FLT3 mutation, occurring in about 25% of newly diagnosed AML patients , this was associated with a particularly unfavorable prognosis, including an increased risk of recurrence and shorter overall survival.
Quizartinib is a second-generation FLT3 inhibitor, an oral small-molecule receptor tyrosine kinase inhibitor that selectively targets FLT3 (FMS-like tyrosine kinase 3). FLT3 is a tyrosine kinase receptor protein normally expressed by hematopoietic stem cells and plays an important role in cell development, promoting cell survival, growth and differentiation through various signaling pathways.
In June 2019, quizartinib (brand name Vanflyta) was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of adult patients with relapsed or refractory FLT3-ITD AML, the first regulatory approval worldwide for the drug . In all countries except Japan, quizartinib is an investigational drug that has not yet been approved.
This NDA is based on the results of the QuANTUM-First trial (NCT02668653). This is a randomized, double-blind, placebo-controlled, global Phase 3 study evaluating quizartinib in combination with standard cytarabine and anthracene in 539 patients aged 18-75 years with newly diagnosed FLT3-ITD-positive AML Cycloid induction and standard cytarabine consolidation chemotherapy, and quizartinib as continuous monotherapy after consolidation. In the trial, patients were randomized 1:1 to two treatment groups to receive quizartinib or placebo in combination with an anthracycline and cytarabine. Eligible patients, including those undergoing hematopoietic stem cell transplantation (HSCT), continued on quizartinib or placebo for up to 36 cycles.
In June, the results of the trial were presented at the 2022 European Association of Hematology Congress (EAH2022). The data showed that the quizartinib regimen reduced the risk of death by 22.4% compared with standard chemotherapy (HR = 0.776 [95% CI: 0.615-0.979]; two-sided p = 0.0324). With a median follow-up of 39.2 months, the quizartinib regimen significantly prolonged overall survival compared with standard chemotherapy (median OS: 31.9 months vs 15.1 months). In this trial, the safety profile of the quizartinib regimen was generally manageable, and no new safety signals were observed.
An application for quizartinib in adults with newly diagnosed FLT3-ITD-positive AML is also under review by regulators in the European Union and Japan, based on results from the QuANTUM-First trial.
“Patients with AML need new targeted therapy options, and the results of the QQuANTUM-First trial demonstrate that quizartinib in combination with standard chemotherapy has the potential to transform the current treatment of patients with the newly diagnosed FLT3-ITD subtype,” said Dr. Ken Takeshita, Global R&D Director, Daiichi Sankyo Pharmaceuticals. The FDA’s priority review of this application reflects the importance of the data, and we will continue to work with the FDA and other global regulatory agencies to support the review of quizartinib in patients with newly diagnosed FLT3-ITD-positive AML.”