Precise treatment of leukemia! Xospata, the second-generation FLT3 inhibitor of Estella, was approved to treat FLT3 mutation recurrence / refractory AML!

January 16, 2020 / BIOON / -- Japanese pharmaceutical company astralas recently announced that Health Canada Canada) has approved xospata (gilteritinib), a daily oral drug, as a single drug therapy for adult patients with recurrent (relapsed) or refractory (drug refractory) acute myeloleukosis (AML) carrying FLT3 mutation (flt3mut +) Xospata has the potential to improve the prognosis of AML patients with two most common mutations: internal tandem repeat (ITD) and tyrosine kinase domain (TKD) mutations in FLT3 transmembrane region It is worth mentioning that xospata is the first and only targeted therapy approved by Health Canada for patients with recurrent or refractory AML carrying FLT3 mutation Xospata's approval also marks the entry of Estella into the field of blood cancer treatment in Canada Dr Andre Schuh, a hematologist and clinical researcher at the Princess Margaret cancer center in Toronto, Canada, said: "AML is a life-threatening cancer with an overall 5-year survival rate of only about 20% in Canada Retreatment of recurrent AML is particularly difficult, especially in the case of FLT3 mutations Xospata's approval is one of the few developments in AML treatment in the past 40 years, providing a new option for patients with FLT3 mutations that may lead to remission and significantly longer survival " AML is a cancer that affects blood and bone marrow If it is not treated, the disease will progress rapidly Once the patient relapses or the drug is difficult to treat, the treatment options will be very limited The incidence rate of AML increased with age The average age of diagnosis in 2016 was 68.5 years old This is the latest year with data available AML is associated with a variety of gene mutations, about 30% of patients can detect FLT3 mutations However, ftl3 mutations in AML patients may change during treatment, even after recurrence Because the prognosis of FLT3 mutant AML is poor, the mutation status of patients should be determined to help determine the best treatment This approval, based on the results of the phase III administrative trial, investigated the efficacy and safety of xospata and salvage chemotherapy in patients with recurrent or refractory flt3mut + AML The results showed that the overall survival time (OS) of xospata group was significantly longer than that of the rescue chemotherapy group (median OS: 9.3 months vs 5.6 months, HR = 0.64 [95% CI: 0.49-0.83], P = 0.0004), the one-year survival rate was doubled (37% vs 17%), and the complete remission rate with complete or partial hematological recovery was doubled (34.0% vs 15.3%) In terms of safety, the most common level 3 adverse events in xospata group were febrile neutropenia (45.9%), anemia (40.7%), thrombocytopenia (22.8%) Xospata belongs to the second generation of FLT3 inhibitors It has inhibitory effect on two different mutations of FLT3 transmembrane internal tandem repeat (ITD) and FLT3 tyrosine kinase domain (TKD) Flt3-itd mutations affect about 30% of AML patients and are associated with worsening disease-free and overall survival Flt3-tkd mutations affect about 7% of AML patients Although the effect of these mutations is not clear, they are associated with therapeutic resistance Xospata is found through research cooperation with Kotobuki Pharmaceutical Co., Ltd of Japan Astaire has the exclusive global right to develop, manufacture and potentially commercialize xospata In the United States, Japan and the European Union, xospata has been granted orphan drug qualification, fast track qualification in the United States and sakigake qualification in Japan In October 2018, xospata was first approved in Japan for the treatment of recurrent or refractory AML adults with FLT3 mutations At the end of November 2018, xospata was approved by the U.S FDA, becoming the first FLT3 targeted preparation for patients with recurrent or refractory AML, which also marks the entry of Astaire into the field of blood cancer treatment in the United States In May 2019, FDA approved a supplementary new drug application (SNDA) of xospata, updated the US product label of xospata, and included the final OS data from phase III Administrative test In the European Union, xospata was approved in October 2019 to treat adult patients with recurrent or refractory AML carrying FLT3 mutation (flt3mut +) In terms of FLT3 inhibitors, rydapt (midostarurin), an anti-cancer drug targeted by Novartis, was approved by FDA in April 2017 to treat adult patients with FLT3 mutation positive newly diagnosed AML, becoming the first target drug for FLT3 mutation positive AML in the world In June 2019, the first three drug targeted anticancer drug vanfllyta (quizartinib, the second generation FLT3 inhibitor) was approved by Japan to treat adult patients with recurrent or refractory flt3-itd AML But in both the US and the EU, vanflyta was denied approval In the key phase III clinical study of quantum-r, compared with salvage chemotherapy, quizartinib oral monotherapy significantly reduced the risk of death by 24% (HR = 0.76, P = 0.0177, 95% CI: 0.58-0.98), and significantly prolonged the overall survival (median OS: 6.2 months [bilateral 95% CI: 5.3-7.2] vs 4.7 months [bilateral 95% CI: 4.0-5.5]) The estimated 1-year survival rate was 27% in the quizartinib group and 20% in the salvage chemotherapy group Original source: Health Canada approves astralas' xospata ® (gilteritinib) for patients with relapsed or refractory acute myeloid leukemia with a FLT3 mutation Fran ç AIS