How does venetoclax treat myelodysplasia?

Venetoclax has shown significant efficacy in the treatment of myelodysplastic syndrome (MDS). On July 21, 2021, the U.S. Food and Drug Administration (FDA) granted venetoclax an emergency approval. Detergent therapy designation (BTD), combined with azacitidine (Azacitidine), is used to treat previously untreated intermediate-risk, high-risk, and very high-risk MDS adult patients. This designation is based on an open-label, multicenter, non-randomized, dose-escalation phase Ib clinical trial (M15-531 study), which evaluated the pharmacokinetics and safety of venetoclax in combination with azacitidine and established the recommended dose and dosing regimen for the Phase 2 trial.

Venetoclax is the world's first new oral targeted drug that specifically targetsBCL-2 protein. It can selectively target and bind to BCL-2 and inhibit its activity, thereby restoring the process of tumor cell apoptosis. Apoptosis is a way to cause tumor cell death. In some blood cancer and solid tumor cells, the BCL-2 protein is highly expressed and inhibits the occurrence of apoptosis. Venetoclax helps promote tumor cell apoptosis by inhibiting BCL-2, thereby achieving the therapeutic effect of MDS.

In the M15-531 study, a total of 57 patients received venetoclax combined with azacitidine. Although the specific efficacy data are not mentioned in detail in the article, the FDA's breakthrough therapy designation is based on the positive interim results of the trial, indicating that the combination therapy has certain efficacy and safety in the treatment of MDS.

Venetoclax combined with azacitidine therapy in treatmentMDS may have better efficacy. Azacitidine is a demethylating drug that can demethylate DNA by inhibiting the activity of DNA methyltransferase and restore the expression of abnormally methylated genes, thus promoting the differentiation and apoptosis of tumor cells. The combination of venetoclax and azacitidine may jointly promote the death of tumor cells through different mechanisms of action and improve the therapeutic effect.