Recently，Ascentage Pharma announced that its proprietary novel Bcl-2 selective inhibitor lisaftoclax (APG-2575) has been approved by China’s National Medical Products Administration (NMPA) for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including Bruton’s tyrosine kinase (BTK) inhibitors, which makes lisaftoclax the first Bcl-2 inhibitor receiving conditional approval and marketing authorization for the treatment of patients with CLL/SLL in China, and the second Bcl-2 inhibitor approved globally.
Lisaftoclax is a proprietary, novel orally administered small-molecule Bcl-2 selective inhibitor developed by Ascentage Pharma to treat patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. In the clinical trials, lisaftoclax has shown broad therapeutic potentials in multiple hematologic malignancies and solid tumors, particularly in CLL/SLL, both as a monotherapy and in combinations.
This approval is based on the results from a pivotal registrational Phase II study (APG2575CC201) that was designed to evaluate the efficacy and safety of lisaftoclax monotherapy in patients with relapsed or refractory CLL/SLL, with the overall response rate (ORR) as the primary endpoint. Lisaftoclax demonstrated compelling efficacy and an ORR that met the prespecified endpoint in patients who previously treated with BTK inhibitors and/or immunochemotherapy. Moreover, lisaftoclax showed a favorable safety profile with no tumor-lysis syndrome (TLS) occurring during the study, a low incidence of hematologic toxicities which were manageable, and a low incidence of non-hematologic toxicities which were mostly grade 1-2.
CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations with over 100,000 new diagnoses reported globally each year1. In China, where the incidence rate of CLL/SLL is lower than that of the western countries, the disease is occurring at a rapidly rising rate, with a younger age of onset and higher aggressiveness2. As the current primary option for the first-line treatment of CLL/SLL, BTK inhibitors have significantly improved treatment outcome for patients. However, BTK inhibitors still face a range of issues such as limited ability to induce deep responses, high risk of relapse in mid-and long-term treatment, toxicities and intolerability associated with prolonged treatment; thus, the need for safer and more effective treatment options for the patients with CLL/SLL.
The introduction of Bcl-2 inhibitors has further revolutionized the treatment of CLL/SLL. The apoptosis suppressor factor Bcl-2, commonly overexpressed in a variety of hematologic malignancies, particularly CLL/SLL, is a key mechanism by which tumor cells evade apoptosis. However, the discovery of Bcl-2 inhibitor as a therapeutic target is highly challenging mainly because its mechanism of action is based on the protein-protein interaction (PPI). The binding interface of Bcl-2 is relatively large, making it difficult for small-molecule inhibitors to exert blocking effects. Additionally, the Bcl-2 protein is located on mitochondria, with double-membrane structure, is among the most complex and challenging cellular components as it requires drugs to first penetrate the cell membrane before they can further act on the mitochondrial membrane. Prior to this, no Bcl-2 inhibitor had been approved for the treatment of CLL/SLL in China. This approval for lisaftoclax fills a treatment gap in CLL/SLL, bringing renewed hope to many patients in the country.
At present, there are still many clinical trials of new anti-cancer technologies in China seeking patients. Consultation on new drugs and technologies, you can contact Beijing South Region Oncology Hospital International Department.
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Post time: Jul-15-2025