Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that lisaftoclax (APG-2575), a novel Bcl-2 inhibitor and one of the company's core assets, has been cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study for treatment of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who were BTKi previously treated . This clearance marks a major step-forward in the global development of lisaftoclax and another important milestone following the approval by the Center for Drug Evaluation (CDE) in China for the registrational Phase II study of lisaftoclax (APG-2575) in patients with relapsed/refractory CLL/SLL (R/R CLL/SLL) in December 2021, as it could potentially pave the way for lisaftoclax to become the second Bcl-2 inhibitor approved anywhere globally.

This global, multi-center, randomized-controlled, registrational Phase III study (APG2575CG301) is designed to assess the efficacy and safety of lisaftoclax (APG-2575) plus a Bruton's tyrosine kinase inhibitor (BTKi) in patients with CLL/SLL who were BTKi previously treated. The study is set to commence in the second half of 2023.

CLL/SLL is the most common form of leukemia in adults, accounting for one-quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses globally every year¹. Despite significant initial responses to current first-line treatments such as immunotherapies, chemotherapies, and BTKis, relapse and drug resistance remain a major clinical challenge. At present, patients with CLL/SLL still have a huge unmet medical need for new treatment options.

Lisaftoclax (APG-2575) is a novel, orally administered small-molecule Bcl-2 selective inhibitor developed by Ascentage Pharma to treat a range of malignancies by selectively blocking the antiapoptotic protein Bcl-2, thus restoring the normal apoptosis process in cancer cells. With strong global best-in-class potential, lisaftoclax (APG-2575) is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal study.

Currently, Ascentage Pharma initiated a total of 19 clinical studies of lisaftoclax (APG-2575) globally, having treated more than 600 patients with the drug thus far, including more than 300 patients with CLL/SLL. In prior studies, lisaftoclax, both as a monotherapy and in combinations, showed clear therapeutic potential as a safe, effective, and easy-to-use therapy for patients with CLL/SLL. According to the initial results from a global Phase II study, lisaftoclax (APG-2575) combined with the next-generation BTKi acalabrutinib achieved encouraging objective response rates (ORRs) in patients with CLL/SLL, including an ORR of 100% (16/16) in treatment-naïve patients and 98% (56/57) in relapsed/refractory patients. In terms of safety, combination regimens demonstrated a safety profile that was on par with lisaftoclax (APG-2575) monotherapy and an extremely low incidence of tumor lysis syndrome (TLS). Furthermore, the study of lisaftoclax (APG-2575) was initiated with a daily dose ramp-up schedule that was friendly to patients and allowed them to quickly reach target doses².

"With progress in the research and development of targeted therapies, we have seen considerable improvement to the survival of patients with CLL/SLL. However, there remain major clinical challenges and urgent unmet medical needs for novel therapies that are safe and effective," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma.  "Lisaftoclax, a key drug candidate of our apoptosis-targeted pipeline with global best-in-class potential, has shown promising efficacy and favorable safety in earlier studies. We are very encouraged by the FDA's clearance for the global registrational Phase III study as it marks a major milestone in the development of lisaftoclax. Fulfilling the mission of addressing unmet clinical needs in China and around the world, we will press ahead with the global registrational Phase III study of lisaftoclax(APG-2575) to allow patients around the world to benefit from this novel therapeutic as soon as possible."