Comparative analysis of venetoclax/venetoclax (venetoclax) alternative drugs and similar drugs

Venetoclax (also known as venetoclax) is a selective BCL-2 inhibitor. It mainly blocks the binding of BCL-2 protein and pro-apoptotic factors, causing tumor cells to lose resistance to death signals, thereby inducing natural cell apoptosis. The drug is widely used in the treatment of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), and is particularly effective in high-risk patients with 17p deletions or TP53 mutations. Due to its accurate efficacy and fewer side effects compared with traditional chemotherapy, venetoclax is considered an important advance in targeted therapy of the blood system. However, some patients may still develop resistance after long-term use of the drug, so research on alternative drugs and similar drugs has attracted much attention.

At present, similar drugs replacing venetoclax are mainly focused on the new generation of BCL-2 inhibitors. Among them, Lisaftoclax (APG-2575) is considered the most promising drug candidate and has entered Phase III clinical trials, showing similar efficacy to venetoclax but better tolerability and lower risk of hematological toxicity. In addition, new molecules such as BGB-11417 (developed by BeiGene) and S64315 (MIK665) are also advancing in international clinical trials, and some results indicate that they may still be effective against venetoclax-resistant tumors. As clinical data on these new drugs continue to accumulate, it is expected to provide more options for patients with hematological tumors in the future.

Drugs in the same class as venetoclax also include MCL-1 inhibitors and BCL-xL inhibitors. The former (such as S64315) can restore sensitivity by acting on another apoptosis signaling pathway when venetoclax is resistant; the latter has a synergistic anti-tumor effect on some leukemia subtypes in experiments. In comparison, venetoclax is safer and more mature. Its common side effects include neutropenia, fatigue and mild nausea, but it is generally more controllable. The new generation of BCL-2 inhibitors may further reduce adverse reactions such as thrombocytopenia in clinical practice.
Taken together, venetoclax is still the core drug for current BCL-2 targeted therapy, but with the emergence of drug resistance problems, future treatments will rely more on combination regimens and molecular precision medication. For example, combining venetoclax with hypomethylating drugs or BTK inhibitors (such as ibrutinib) can significantly extend patients' progression-free survival. For patients with drug resistance or intolerance, Lisaftoclax and other similar drugs may be considered as an alternative. In the future, the BCL-2 family multi-target combined inhibition strategy will become a new trend in the treatment of leukemia and lymphoma, bringing more durable and safe treatment options to patients.
Reference: https://www.drugs.com/