Ascentage Pharma's Lisaftoclax Receives Priority Review in China for Relapsed/Refractory CLL/SLL

Ascentage Pharma (搜索)搜索该词条 has announced that the New Drug Application (NDA) for lisaftoclax查看药品详情 (APG-2575查看药品详情), a novel Bcl-2 (搜索)搜索该靶点 selective inhibitor, has been accepted and granted Priority Review designation by the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA). The application seeks approval for the treatment of patients with relapsed or refractory (r/r) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL (搜索)搜索该疾病). This marks a significant step as it is the first NDA for a domestically developed Bcl-2 inhibitor in China and could potentially make lisaftoclax the second Bcl-2 inhibitor approved globally.

The NDA is based on data from a pivotal registrational Phase II study conducted in China (APG2575CC201), which assessed the efficacy and safety of lisaftoclax查看药品详情 in patients with r/r CLL/SLL (搜索)搜索该疾病. The study's primary endpoint was the overall response rate (ORR).

Addressing Unmet Needs in CLL/SLL Treatment

CLL/SLL (搜索)搜索该疾病, a hematologic malignancy arising from mature B-cell neoplasms, predominantly affects older individuals. While less prevalent in China compared to Western countries, its incidence is increasing with a trend towards younger onset and greater aggressiveness. Current treatments, including immunotherapies and Bruton's tyrosine kinase inhibitors (BTKis), have improved initial responses, but limitations persist, leading to poor prognosis, reduced quality of life, and disease complexity. Consequently, there is a critical need for new, effective, and safe treatment options for patients with r/r CLL/SLL.

The Role of Bcl-2 Inhibition

The introduction of Bcl-2 (搜索)搜索该靶点 inhibitors has transformed CLL/SLL (搜索)搜索该疾病 treatment. Bcl-2, an apoptosis suppressor, regulates cell survival by controlling mitochondrial membrane permeability. Overexpression of Bcl-2, a common feature in hematologic malignancies like CLL/SLL, allows tumor cells to evade apoptosis. Lisaftoclax查看药品详情 selectively blocks the antiapoptotic protein Bcl-2, restoring normal apoptosis in cancer cells.

Challenges in Targeting Bcl-2

Developing Bcl-2 (搜索)搜索该靶点 inhibitors is challenging due to the protein-protein interaction (PPI) mechanism, where the binding interface is large, making it difficult for small-molecule inhibitors to exert blocking effects. Additionally, the mitochondrial membrane location adds complexity. Despite these challenges, lisaftoclax查看药品详情 has demonstrated compelling clinical benefit and entered a pivotal registrational study.

Lisaftoclax: A Potential New Treatment Option

Lisaftoclax查看药品详情 is an investigational, orally administered small-molecule Bcl-2 (搜索)搜索该靶点 selective inhibitor. It is currently being evaluated in multiple registrational Phase III studies, including:

• A global Phase III study of lisaftoclax in combination with a BTKi in previously treated patients with CLL/SLL.
• A global Phase III study of lisaftoclax in combination with acalabrutinib for the first-line treatment of treatment-naïve patients with CLL/SLL.
• A global 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 Phase III study of lisaftoclax in combination with AZA for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS).

"This NDA submission for lisaftoclax查看药品详情 could potentially pave the way for lisaftoclax to become the first approved China-developed Bcl-2 (搜索)搜索该靶点 inhibitor," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma (搜索)搜索该词条.