Astellas Gilteritinib Obtains NMPA Conditional Approval

- Feb 21, 2021-

On February 4, 2021, Astellas Pharmaceutical Group (TSE: 4503) announced today that the China National Medical Products Administration (NMPA) has conditionally approved XOSPATA® (gilteritinib fumarate tablets, collectively referred to as gilteritinib) for therapeutic use Well-validated testing methods have detected relapsed (relapsed disease) or refractory (treatment resistant) acute myeloid leukemia (AML) adult patients with FMS-like tyrosine kinase 3 (FLT3) mutations. Gilteritinib was granted priority review by the National Medical Products Administration of China in July 2020, and was included in the third batch of clinically needed overseas new drugs in November 2020. Under the accelerated channel, it has now been approved.


Professor Ma Jun, Director of the Harbin Institute of Hematology and Cancer, China, pointed out: “Patients with relapsed or refractory acute myeloid leukemia with FLT3 mutations urgently need new treatment options. As China’s first approved treatment for relapsed or refractory FLT3 mutations Gilteritinib, a targeted therapeutic drug for acute myeloid leukemia, has been approved under the accelerated channel, allowing Chinese patients to quickly obtain innovative treatment options."


Gilteritinib has been shown to have a significant inhibitory effect on two types of FLT3 mutations, namely FLT3 internal tandem duplication (FLT3-ITD) and FLT3 tyrosine kinase domain (FLT3-TKD). FLT3-ITD mutation affects about 30% of patients with acute myeloid leukemia, which has a higher risk of recurrence and a shorter overall survival than wild-type FLT3. The FLT3-TKD mutation affects approximately 7% of patients with acute myeloid leukemia3. During the treatment of acute myeloid leukemia, even after recurrence, the status of FLT3 mutation may change. Therefore, confirming the status of the patient's FLT3 mutation at the time of relapse will help determine the appropriate and potential target treatment.


Professor Wang Jianxiang, deputy director of the Institute of Hematology, Chinese Academy of Medical Sciences, said: “The FLT3 mutation has a very negative impact on the prognosis of patients with acute myeloid leukemia. With the support of sufficient efficacy and safety data, the use of gilteritinib is approved, which is a domestic FLT3 mutation. The number of patients with relapsed or refractory acute myeloid leukemia provides an important new option."

Professor Wu Depei, chairman of the Hematology Branch of the Chinese Medical Association, said: "The diagnosis and treatment of hematological malignancies has developed rapidly in recent years. The application of a variety of new drugs/therapies has brought some diseases, such as lymphoma and myeloma, into the era of'no chemotherapy'. Gilteritinib is approved to treat relapsed or refractory acute myeloid leukemia with FLT3 mutation, and will also promote the treatment of acute myeloid leukemia to the era of'no chemotherapy'."


Acute myeloid leukemia is a tumor that affects the blood and bone marrow, and its incidence increases with age. Acute myeloid leukemia is one of the most common leukemias in adults. It is estimated that approximately 80,000 people in China are diagnosed with leukemia each year.


Dr. Andrew Krivoshik, Senior Vice President of Oncology Development and Head of Global Therapy of Astellas said: “Patients with relapsed or refractory acute myeloid leukemia with FLT3 mutations urgently need new treatments. They are now saving their lives after chemotherapy. The median survival time is less than 6 months. The accelerated approval of gilteritinib is an important step in providing new treatment options for Chinese doctors and patients. Astellas is committed to developing innovative breakthroughs for refractory tumors with limited treatment options The approval of gilteritinib in China is part of our commitment, and we look forward to it very much.”


The above approval is based on the results of the Phase III ADMIRAL trial, which has been published in the New England Journal of Medicine. Compared with patients receiving salvage chemotherapy, gilteritinib treatment can significantly prolong overall survival (OS). The median overall survival of patients treated with gilteritinib was 9.3 months, while that of patients receiving salvage chemotherapy was 5.6 months [hazard ratio = 0.64 (95% CI 0.49, 0.83), P=0.0004]. Additional Chinese patient pharmacokinetic data is derived from the ongoing Phase III COMMODORE trial, which has also been reviewed.


The safety of gilteritinib was evaluated in 319 patients with relapsed or refractory acute myeloid leukemia who received at least one dose of 120 mg of gilteritinib per day and carried FLT3 mutations11. The most common adverse reactions (incidence ≥ 10%) of all grades after receiving gilteritinib were alanine aminotransferase (alanine aminotransferase, ALT) increase (25.4%), aspartate aminotransferase (aspartate aminotransferase, AST increase) High (24.5%), anemia (20.1%), thrombocytopenia (13.5%), neutropenic fever (12.5%), reduced platelet count (12.2%), diarrhea (12.2%), nausea (11.3%) ), increased blood alkaline phosphatase (11%), fatigue (10.3%), decreased white blood cell count (10%), and increased blood creatine phosphokinase (10%). One case occurred in patients receiving gilteritinib Adverse reaction differentiation syndrome leading to death. The most common serious adverse reactions (incidence ≥ 3%) are neutropenic fever (Febrile Neutropenia, 7.5%) and elevated alanine aminotransferase (ALT) ( 3.4%), and aspartate aminotransferase (AST) increased (3.1%). Other serious adverse reactions of clinical significance include prolonged QT interval of electrocardiogram (0.9%) and reversible posterior encephalopathy syndrome (0.3%). %).


About Gilteritinib

Gilteritinib is a drug discovered through research cooperation between Astellas and Kotobuki Pharmaceutical Co., Ltd. Astellas has the exclusive right to develop, manufacture and commercialize gilteritinib worldwide. Gilteritinib (trade name: Xospata®) has been accessible to patients in the United States, Japan, some EU countries and other countries and regions, and is used to treat adult patients with relapsed or refractory acute myeloid leukemia carrying FLT3 mutations. .


Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor, which has a significant inhibitory effect on FLT3-ITD and FLT3-TKD mutations. FLT3-ITD is a common driver mutation, which leads to high disease burden and poor prognosis.