FDA Grants Priority Review for Acute Myeloid Leukemia Drug

The FDA has accepted Daiichi Sankyo’s new drug application (NDA) of quizartinib to treat adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3-ITD positive. The application has been granted priority review with a Prescription Drug User Fee Act date (PDUFA) of April 24, 2023. If approved, quizartinib will be used in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation.

Mutations of the FLT3 gene occur in about 30% of AML patients. FLT3-ITD (internal tandem duplication) is the most common type of FLT3 mutation in AML and is associated with increased risk of relapse and shorter overall survival. The conventional treatment for newly diagnosed AML is intensive chemotherapy with hematopoietic stem-cell transplantation for eligible patients.

The NDA is based on data from the QuANTUM-First phase 3 trial in which quizartinib was combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy. Results were presented Presidential Symposium of the European Hematology Association (EHA) 2022 Congress. The trial, which enrolled 539 patients, demonstrated a 22.4% reduction in the risk of death compared with standard chemotherapy alone in adult patients with newly diagnosed FLT3-ITD positive AML. After a median follow-up of 39.2 months, median overall survival was more than double at 31.9 months for patients receiving quizartinib compared with 15.1 months for patients receiving chemotherapy.

Ken Takeshita, M.D.

The safety of quizartinib was generally manageable with no new safety signals observed. Rates of grade 3 or higher treatment emergent adverse events (TEAEs) were similar for both study groups and the most common grade 3 or higher treatment emergent adverse events occurring in ≥ 10% of patients were febrile neutropenia, neutropenia, hypokalemia and pneumonia. Rates of TEAEs associated with fatal outcomes were 11.3% for quizartinib versus 9.7% chemotherapy alone and were mainly due to infections.

“There is a need for new targeted therapy options for patients with acute myeloid leukemia and the results of the QuANTUM-First trial showed that quizartinib in combination with standard chemotherapy has potential to change the current standard of care for newly diagnosed patients with the historically difficult-to-treat FLT3-ITD subtype,” Ken Takeshita, M.D., global head of R&D at Daiichi Sankyo, said in a press release.