Ascentage Pharma has announced that the China National Medical Products Administration (NMPA) has accepted its New Drug Application (NDA) for lisaftoclax (APG-2575), a novel Bcl-2 selective inhibitor, and recommended it for Priority Review. The application seeks approval for the treatment of patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This marks a significant step as it is the first NDA for a domestically developed Bcl-2 inhibitor in China, potentially making lisaftoclax the second Bcl-2 inhibitor approved globally.
The NDA is based on the results of a pivotal registrational Phase II study (APG2575CC201) conducted in China. The study evaluated the efficacy and safety of lisaftoclax in patients with r/r CLL/SLL, with the primary endpoint being the overall response rate (ORR).
The Need for New CLL/SLL Treatments
CLL/SLL, a hematologic malignancy arising from mature B-cell neoplasms, predominantly affects older individuals. While it is among the most common leukemia subtypes in the Western world, its incidence is rapidly increasing in China, with a trend towards younger onset and higher aggressiveness. Current treatments, including immunotherapies and Bruton's tyrosine kinase inhibitors (BTKis), have improved initial treatment responses. However, limitations of existing options lead to poor prognosis, reduced quality of life, and high disease complexity, creating an urgent need for safe and effective new treatments for patients with r/r CLL/SLL.
Lisaftoclax: A Selective Bcl-2 Inhibitor
Lisaftoclax is an orally administered small-molecule Bcl-2 selective inhibitor designed to selectively block the antiapoptotic protein Bcl-2, thereby restoring normal apoptosis in cancer cells. The overexpression of Bcl-2 is a key mechanism by which tumor cells evade apoptosis, particularly in hematologic malignancies like CLL/SLL. Lisaftoclax has demonstrated compelling clinical benefit and has entered a pivotal registrational study, positioning it as a potential treatment option for various hematologic malignancies and solid tumors, both as a single agent and in combination therapies.
Ongoing Phase III Studies
Lisaftoclax is currently being evaluated in multiple registrational Phase III studies. These include:
- A global registrational Phase III study of lisaftoclax in combination with a BTKi in previously treated patients with CLL/SLL.
- A global registrational Phase III study of lisaftoclax in combination with acalabrutinib for the first-line treatment of treatment-naïve patients with CLL/SLL.
- A global registrational Phase III study of lisaftoclax in combination with azacitidine (AZA) for the first-line treatment of elderly/unfit treatment-naïve patients with acute myeloid leukemia (AML) who were intolerant of standard induction chemotherapies.
- A global registrational Phase III study of lisaftoclax in combination with AZA for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS).
Ascentage Pharma's Commitment
"Ascentage Pharma's founding team has over 20 years of deep experience in developing apoptosis-targeted therapies and has made significant strides with the Bcl-2 target," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. He emphasized the challenges in developing Bcl-2 inhibitors, noting that only one has been approved globally to date. "This NDA submission for lisaftoclax could potentially pave the way for lisaftoclax to become the first approved China-developed Bcl-2 inhibitor, thus marking another major milestone that is a culmination of the Ascentage Pharma's deep commitment and perseverant work in the past 15 years."
