Can enasidenib and venetoclax be used together?

Enasidenib and Venetoclax are two different anti-cancer drugs used to treat different types of leukemia. Ensidipine is mainly used to treat acute myeloid leukemia (AML) with mutations in the IDH2 gene, while venetoclax is mainly used to treat chronic lymphocytic leukemia (CLL), but in some cases venetoclax can also be used to treat newly diagnosed AML.

Ensidipine is the first mutant IDH2 inhibitor to induce differentiation of IDH2 mutant leukemic cells. However, the clinical efficacy of ensidipinemonotherapy in relapsed or refractory (R/R) acute myeloid leukemia (AML) is limited, emphasizing the need for combination therapy. Preclinical studies have shown that IDH-mutated leukemia cells are particularly sensitive to venetoclax's inhibition of BCL2, a finding supported by clinical studies of venetoclax's combination therapy. Previous studies have shown that in a xenograft model of patients with IDH2-mutated acute myeloid leukemia, the combination of ensidipine and venetoclax was more effective than either drug alone.

Preliminary safety and efficacy results from an ongoing, open-label, single-arm, Phase Ib/II trial (NCT04092179) of ensidipine plus venetoclax in patients with IDH2-mutated myeloid malignancies. The results showed9 AML patients completed at least 1 cycle of treatment and were considered evaluable for efficacy. One AML patient died of intracranial hemorrhage before the end of cycle 1. The median observation time was 3.5 months. Among evaluable patients, 2 patients achieved CR (22%) and 3 patients achieved CRi (33%), with an ORR of 55%. The median number of remission cycles was 3. To date, all responders remain in remission and on the study, having received a median number of six cycles. Among the remaining 4 patients, 2 patients had stable disease and 2 patients experienced disease progression and died (one died after 7 cycles and the other died after 1 cycle). The median OS for the entire cohort has not yet been reached.

Ensidipine plus venetoclax was a well-tolerated regimen, with no dose-limiting toxicities observed at the current dose levels. Preliminary efficacy of this combination is encouraging, with an ORR of 55% in evaluable R/R AML patients and some responders achieving deep molecular responses. No patient discontinued the study due toadverse events.

In summary, ensidipine and venetoclax can be used together in certain circumstances, but this needs to be done under the guidance of a doctor, and patients should be closely monitored by their doctor to ensure safety and effectiveness.

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. For more information on overseas drug prices and specific information, please consult Yaode Medical Consultant.