NEW YORK – The US Food and Drug Administration on Thursday approved Daiichi Sankyo's Vanflyta (quizartinib) in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, followed by maintenance monotherapy, as a treatment for patients with newly diagnosed FLT3-internal tandem duplication-positive acute myeloid leukemia.
Concurrently, the FDA approved Invivoscribe's LeukoStrat CDx FLT3 Mutation Assay for identifying AML patients with FLT3-ITD mutations who are eligible for Vanflyta. The PCR-based test runs on Thermo Fisher Scientific's Applied Biosystems 3500xL Dx Genetic Analyzer and detects internal tandem duplication (ITD) and tyrosine kinase domain mutations D835 and I836 in the FLT3 gene in peripheral blood or bone marrow aspirates of AML patients.
The agency approved the treatment after reviewing results from the Phase III QuANTUM-First trial, in which newly diagnosed AML patients received Vanflyta plus standard chemotherapy as an initial treatment, followed by maintenance monotherapy. In the trial, the risk of death was reduced by 22 percent for patients on Vanflyta compared to standard chemotherapy. According to Daiichi Sankyo, this is the first data showing Vanflyta plus chemo improves overall survival.
Complete response rates were similar in both arms of the trial. However, the median duration of complete response was 38.6 months in the Vanflyta arm compared to 12.4 months in the comparator arm.
As many as 37 percent of newly diagnosed patients with AML have FLT3 gene mutations, and about 80 percent of those are FLT3-ITD mutations.
"Patients with the FLT3-ITD subtype of AML can now be treated with the first ever FLT3 inhibitor approved across the three phases of treatment these patients typically receive," Daiichi Sankyo President and CEO Ken Keller said in a statement.
The latest approval does not apply to the use of Vanflyta monotherapy after patients have gotten an allogeneic hematoipoietic stem cell transplant, since no overall survival benefit has been demonstrated in that setting. The drug's label also includes a boxed warning about the risk of treatment-related QT prolongation, torsades de pointes, and cardiac arrest, and as such, Vanflyta will be available with a risk evaluation and mitigation strategy.
Based on earlier data from the QuANTUM-First trial, Japanese regulators approved Vanflyta in 2019 for adults with relapsed or refractory, FLT3-ITD-positive AML alongside the LeukoStrat assay as a companion diagnostic.