Enasidenib is the first generation AML targeted therapy drug

Enasidenib is an oral small molecule IDH2 inhibitor, mainly used to treat patients with relapsed or refractory acute myeloid leukemia (AML) with IDH2 mutations. Under normal circumstances, the IDH2 protein is involved in cellular metabolic processes, but once mutated, it will abnormally produce 2-hydroxyglutarate (2-HG). This metabolic product can cause cell differentiation to be blocked. Ensidipine inhibits the mutant IDH2 protein and reduces the level of 2-HG, thereby promoting the redifferentiation of leukemia cells into normal hematopoietic cells.

In the development of targeted therapy for AML, the first generation mainly includes non-selective drugs such as FLT3 inhibitors (such as sorafenib). The second generation includes molecular precision drugs such as ensidipine that target specific gene mutations (such as IDH1/2, FLT3, etc.). Therefore, ensidipine is widely considered to be one of the representatives of the second generation of AML targeted therapy drugs. Its development and marketing mark that AML treatment has entered the era of more precise molecular classification.

Compared with the first-generation broad-spectrum kinase inhibitors, ensidipine has higher targeting and better tolerability. Compared with similar IDH mutation-targeting drugs, such as the IDH1 inhibitor ivosidenib (Ivosidenib), ensidipine focuses on the IDH2 mutation population. In addition, it does not rely on cytotoxic mechanisms, but works by inducing cell differentiation, so the side effects are relatively mild, and it is especially suitable for elderly AML patients who are frail or intolerant to chemotherapy.

Ensidipine has been approved by the U.S.FDA for the treatment of adult patients with relapsed or refractory IDH2mutatedAML. In actual clinical practice, it is a part of AML that lacks treatment optionsIt brings new hope to patients, especially those who cannot tolerate intensive chemotherapy. In the future, ensidipine is also expected to be used in combination with other targeted drugs or low-intensity chemotherapy to further improve the treatment effect and open up broader prospects for precision treatment of AML.

Reference materials:https://www.idhifa.com/