The leukemia targeted drug Gilteritinib has been launched in China, and its clinical efficacy and medication methods are explained in detail

Gilteritinib was developed by Japan's Astellas Pharmaceutical Company. As a FLT3 inhibitor, it is effective against both FLT3-ITD and FLT3-TKD mutations. From being initially found to significantly prolong the overall survival of patients with acute myeloid leukemia, to now showing strong anti-tumor effects in the treatment of other tumors, giritinib is transcending its original therapeutic field. For domestic patients, although this drug has been on the market, it has not yet been included in the medical insurance system, and the financial burden is still heavy. The price of genuine giritinib in the domestic market is about 20,000 to 30,000 yuan per box, but in overseas markets, especially the generic version in Laos, the price is only between 2,000 and 5,000 yuan, and the drug ingredients are basically the same as the original drug.

01 Therapeutic Breakthrough

The development of Gilteritinib (Gilteritinib) marks an important breakthrough in the treatment of acute myeloid leukemia. As the world's first targeted drug approved for the treatment of relapsed or refractory AML with FLT3 mutations, it brings a new option for precision treatment.

In AML, FLT3-ITD mutations and FLT3-TKD mutations are the two main types of adverse prognostic mutations. The former accounts for about 20-25% and the latter accounts for about 5-10% . As a I type inhibitor, giritinib is effective against both mutations. This is the main difference between it and II type FLT3 inhibitors. The globalIIIphaseADMIRAL study shows that compared with traditional salvage chemotherapy, giritinib alone is more effective in relapse/RefractoryFLT3mutatedAML patients have experienced better response rates and overall survival.

02 New discoveries in solid tumors

The new discovery of giritinib in the treatment of solid tumors has demonstrated its therapeutic potential in a wider range of fields.

A latest study from Gannan Medical University shows that giritinib exhibits significant anti-tumor activity in AXL positive esophageal cancer, ovarian cancer and gastric cancer cells.

This study published in "Cell Death Discovery" revealed that geritinib significantly inhibited the proliferation, migration and invasion abilities of these tumor cells by inducing apoptosis and cell cycle arrest.

Mechanistically, giritinib treatment down-regulates multiple cancer-related pathways, including the mTOR pathway, the p53 pathway, and the Wnt pathway.

The research team found that giritinib showed strong anti-tumor effects in vitro, explants and in vivo models, providing new treatment possibilities for patients with AXL positive solid tumors.

03 Asian patients benefit

The COMMODORE study provides us with valuable data on the use of giritinib in Asian patients.

This phase III study, which was mainly conducted in Asia, included 234 patients, of which 85.9% were from Asia and 64.5% were from China.

The results of the median follow-up10.3 months showed that the median overall survival of the geritinib group was significantly better than that of the salvage chemotherapy group, reaching a difference of 9.6 months versus 5.0 months.

In addition, the composite complete response rate was higher in the geritinib arm and a higher proportion of patients received a transplant.

Encouragingly, the study confirmed the safety advantage of gilitinib, after exposure adjustment≥3The incidence of grade adverse events was lower.

04 MRDGuide Treatment

FLT3-ITDMeasurable residual disease has become an important indicator to guide geritinib treatment. The discovery provides a powerful tool for precision medicine, helping doctors determine which patients are most likely to benefit from treatment.

RandomizedPhase III studyBMT CTN 1506Shows that maintenance therapy with geritinib is associated with an improvement in relapse-free survival (RFS) in patients with detectable MRD in the peritransplantation period, but not in those without detectable MRD.

The analysis showed that the MRD levels detected by the highly sensitive detection method were significantly related to both RFS and the risk of recurrence. This provides a basis for individualized treatment.

The Hematology Hospital of the Chinese Academy of Medical Sciences has developed the domestically leading FLT3-ITD MRD detection method, with a sensitivity of 10⁻⁵-10⁻⁶.

05 Exploration of combination therapy

Combination therapy is an important direction to improve the efficacy of FLT3mutatedAML patients. Professor Wei Hui’s team is conducting research on triple therapy.

Foreign studies have shown that hypomethylating drugs, BCL-2 inhibitors combined with giritinib have shown good efficacy in the treatment of FLT3 mutationsAML.

Among the enrolled patients, especially those who are very refractory to treatment, traditional chemotherapy drugs are almost ineffective, but the three-drug treatment regimen has achieved good remission effects.

With these combination regimens, patients can achieve deeper remissions, with minimal residual disease levels reaching 10⁻⁵ after one course of treatment.

06 Price and access

The price of giritinib varies significantly, providing patients with different options. Economic accessibility is always an unavoidable practical issue in anti-cancer treatment.

1. Domestic market price: Giritinib has been launched in China under the trade name Sigattan, but it has not yet been included in the national medical insurance catalog.

The domestic market price varies significantly according to different specifications: 40mg Since it is not covered by medical insurance, the patient needs to pay the full amount out of pocket.

2.International market price comparison: In overseas markets, the price difference is more significant. The Hong Kong version of the original drug sells for about 90,000 yuan per box of 42 tablets, and the European version of 84 tablets costs even more than 200,000 yuan.

3. Generic drug selection: Laos has become the main producer of generic drugs of giritinib. Several pharmaceutical companies, including Lucius Pharmaceuticals, Daewoong Pharmaceuticals, and ASEAN Pharmaceuticals, have produced generic versions of giritinib.

The price of generic drugs in Laos is close to the people. Take the 40mg×90 tablets produced by Lucius Pharmaceuticals as an example. The price is only about more than 2,000 yuan. ASEAN Pharmaceutical's 40mg×84 tablets are priced at 4,000-5,500 yuan, while Daxiong Pharmaceutical's similar specifications sell for about more than 4,000 yuan.

The main pharmaceutical ingredients of these generic drugs are basically the same as the original drugs, and have been approved by the Lao Ministry of Health.

07 Correct medication and precautions

Oral once daily, 120 mg each time. Swallow the tablet whole. Do not break, crush or chew.

Because drug response may be delayed, treatment is recommended for at least6 months in the absence of disease progression or unacceptable toxicity to allow sufficient time for clinical response to develop.

In terms of adverse reaction management, myalgia/arthralgia, elevated transaminases, and fatigue/discomfort are common side effects. More serious but less common adverse reactions include differentiation syndrome, reversible posterior encephalopathy syndrome, electrocardiographic QT interval prolongation, and pancreatitis.

Special attention should be paid to the fact that giritinib may cause fetal harm. Women of childbearing potential should use effective contraceptive measures during treatment and for at least6 months after the last dose.

For domesticAML patients, obtaining giritinib means a monthly financial burden of tens of thousands of yuan, while Lao generic drugs reduce this cost to thousands of yuan.

The story of gilitinib is not over yet. Looking to the future, three-drug combination therapy and MRD detection methods can be more widely used and produce more research results, benefiting more AML patients. As gilitinib continues to be explored in the field of solid tumors, this drug may bring hope to more cancer patients.

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References:

1.Global pivotal clinical studies:Perl AE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019.

2.Asian patient data:Wang J, et al. Gilteritinib vs salvage chemotherapy in Asian patients with relapsed/refractory FLT3-mutated AML. Lancet Haematol. 2022.

3.Solid tumor potential research:Li Z, et al. Gilteritinib induces apoptosis and cell cycle arrest in AXL-positive esophageal, ovarian, and gastric cancers. Cell Death Discov. 2024.

4.Drug supervision and information: China National Medical Products Administration (NMPA) Drug Approval Information