FDA Notifies Daiichi that PDUFA Date for Quizartinib in AML Extended by Three Months

Rare Daily Staff

The U.S. Food and Drug Administration has extended the review period by three months for Daiichi’s New Drug Application of quizartinib for certain patients with the rare blood cancer acute myeloid leukemia.

Daiichi is seeking approval of quizartinib in combination with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and as continuation monotherapy following consolidation, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML).

The FDA is now expected to act on the application by July 24, 2023. The delay is intended to allow additional time to review requested updates to the proposed Risk Evaluation and Mitigation Strategies  included in this application. No additional efficacy or safety data has been requested.

More than 474,500 new cases of leukemia were reported globally in 2020 with more than 311,500 deaths. AML accounts for 23.1 percent of total leukemia cases worldwide and is most common in adults. In the United States an estimated 20,380 new cases of AML will be diagnosed in 2023 with the five-year survival rate reported at 30.5 percent. A number of gene mutations have been identified in AML, and FLT3 (FMS-like tyrosine kinase 3) mutations are the most common, observed in up to 37 percent of all newly diagnosed patients.

Approximately 80 percent of FLT3 mutations in AML are FLT3-ITD (internal tandem duplications), an oncogenic driver mutation that presents with a high leukemic burden. Patients with FLT3-ITD positive AML tend to have a particularly unfavorable prognosis including increased risk of relapse and shorter overall survival. The five-year survival rate for patients with FLT3-ITD positive AML has been reported at approximately 20 percent. The conventional treatment for fit patients with newly diagnosed AML is intensive induction and consolidation chemotherapy, with or without targeted therapy, and HSCT for eligible patients.

Quizartinib is an oral, highly potent type II FLT3 inhibitor that selectively targets FLT3-ITD mutations and has been specifically developed for patients with FLT3-ITD positive AML. Regulatory applications for quizartinib in newly diagnosed FLT3-ITD positive AML are currently under review in Europe, Japan and the U.S. based on the results of the QuANTUM-First trial. The FDA has granted Priority Review and Fast Track designation to quizartinib for the treatment of adult patients with newly diagnosed AML that is FLT3-ITD positive in combination with standard cytarabine and anthracycline induction and cytarabine consolidation chemotherapy. Orphan Drug designation has been granted to quizartinib for the treatment of AML in Europe, Japan, and the United States.

Quizartinib is approved for use in Japan for the treatment of adult patients with relapsed/refractory AML that is FLT3-ITD positive, as detected by an approved test.

The application is based on results from the QuANTUM-First trial, a phase 3 study that demonstrated that quizartinib combined with standard cytarabine and anthracycline induction and standard cytarabine consolidation chemotherapy, and continued as monotherapy following consolidation, resulted in a statistically significant and clinically meaningful improvement in overall survival in adult patients with newly diagnosed FLT3-ITD positive AML compared to chemotherapy alone. The results of QuANTUM-First were presented at the 2022 European Hematology Association Congress.

The safety of quizartinib combined with intensive chemotherapy and as continuation monotherapy in QuANTUM-First was generally manageable with no new safety signals observed. The incidence of grade ≥3 QT prolongation events was low, with uncommon ventricular arrythmia events. Overall, the risk of QT prolongation was manageable with ECG monitoring, quizartinib dose modification and correction/elimination of additional risk factors.

“Quizartinib was shown to improve overall survival when added to standard chemotherapy and continued as monotherapy and has potential to change the standard of care for patients with newly diagnosed FLT3-ITD positive AML,” said Mark Rutstein, global head, Oncology Clinical Development for Daiichi Sankyo.

Photo: Mark Rutstein, global head, Oncology Clinical Development for Daiichi Sankyo.