Preparation of Enasidenib

Enasidenib is an oral, selective, and potent small molecule inhibitor of mutant isocitrate dehydrogenase 2 (id H2). Neomorphic mutations in IDH2 are frequently found in hematological malignancies and solid tumors and lead to the production of the oncometabolite (R)-2-hydroxyglutarate. Elevated levels of (R)-2-hydroxyglutarate lead to histone and DNA methylation, which is associated with blocked differentiation and tumorigenesis. In PDX mice transplanted with human IDH2 mutant acute myeloid leukemia cells, ensidipine treatment resulted in normalization of (R)-2-hydroxyglutarate serum levels, leukemic blast differentiation, and increased survival.

Early clinical data in patients with relapsed/refractory IDH2 mutant acute myeloid leukemia show that in approximately 20% of cases, ensidipine is well tolerated and induces durable complete remissions as a single agent. A significant drug-related side effect is differentiation syndrome. Based on these results, the compound was recently approved in the United States for the treatment of relapsed/refractory id H2-mutant acute myeloid leukemia.

Encidipine research medicine is not currently on the market in China, so it cannot be included in medical insurance. The price of ensidipine plain medicine when it is launched overseas is very high, and the price of each box may be around 30,000 yuan (the price may fluctuate due to the exchange rate). Currently, there are cheaper generic ensidipine drugs produced by other pharmaceutical companies overseas. For example, the price of Specification50mg*30 tablets produced by a Laos pharmaceutical factory may be more than 2,000 yuan per box (the price may fluctuate due to the exchange rate). Its pharmaceutical ingredients are basically the same as those of the original drugs sold abroad.