Astellas’ FLT3 Inhibitor Gilteritinib Tablet Included in CDE’s Priority Review List for Relapsed/Refractory FLT3-Mutated AML

Source | Medical Horizon

According to the latest public notice on the website of the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration (NMPA), Astellas’ gilteritinib fumarate tablets were included in the proposed priority review list on July 21, on the grounds that they “meet the criteria for drugs eligible for conditional approval.” Gilteritinib is a next-generation FLT3 tyrosine kinase inhibitor that has been approved for marketing in multiple countries and regions, including the United States, Japan, and Europe, for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring FLT3 mutations. Notably, gilteritinib has been granted Fast Track designation, Orphan Drug designation, and Priority Review designation by the U.S. Food and Drug Administration (FDA).

Screenshot source: CDE official website

Gilteritinib is a next-generation FLT3 tyrosine kinase inhibitor (TKI) co-developed by Astellas and Kotobuki Pharmaceutical Co., Ltd. It is an oral, once-daily therapy indicated for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML) harboring FLT3 gene mutations. Astellas holds exclusive global rights for the development, manufacturing, and commercialization of this drug.

Preclinical studies have demonstrated that gilteritinib can inhibit two common FLT3 mutations found in approximately one-third of patients with acute myeloid leukemia (AML): FLT3-ITD and FLT3-TKD. FLT3-ITD is a prevalent driver mutation associated with high disease burden and poor prognosis. Meanwhile, gilteritinib can sustain the inhibition of FLT3 activity in vivo and is less likely to cause myelosuppression. It also inhibits the receptor tyrosine kinase Axl, thereby blocking a potential mechanism by which tumor cells develop resistance.

Currently, gilteritinib has been approved for marketing in the United States, Japan, Canada, Brazil, and multiple European countries for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring FLT3 mutations. In the United States, the FDA has granted gilteritinib Fast Track designation, Orphan Drug designation, and Priority Review designation.

In China, the marketing application for gilteritinib was accepted in April this year. According to a press release previously issued by Astellas, the indication sought for gilteritinib in China is for the treatment of adult patients with relapsed or refractory (treatment-resistant) acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3mut+). The drug has been included in the proposed priority review on the grounds that it “meets the criteria for drugs eligible for conditional approval.” This suggests that the drug is poised for accelerated approval in China.

Acute myeloid leukemia (AML) is a malignant blood cancer caused by the malignant transformation of bone marrow hematopoietic stem and progenitor cells. Activating mutations in the FLT3 tyrosine kinase gene are the most frequent genetic alterations in patients with AML, affecting approximately 30% of AML patients. Patients with FLT3 mutation-positive acute myeloid leukemia have a very poor prognosis, with a median overall survival of less than 6 months following salvage chemotherapy, highlighting an urgent need for new treatment options.

References

[1] Official website of the China National Medical Products Administration and the Center for Drug Evaluation. Retrieved Jul 21, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=20

[2] Astellas Announces Acceptance of Marketing Application for XOSPATA® (gilteritinib) by China’s National Medical Products Administration. Retrieved April 10, 2020, from https://mp.weixin.qq.com/s/K_QUyk17q7vo0VHmFPrICA

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