Ascentage Pharma Marks Lisaftoclax Approval by China NMPA, Revolutionizing CLL/SLL Therapy

Ascentage Pharma, a global biopharmaceutical company focused on addressing unmet medical needs in cancers, has announced that its proprietary novel Bcl-2 selective inhibitor, lisaftoclax (APG-2575), has received approval from China’s National Medical Products Administration (NMPA). This approval is for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously undergone at least one systemic therapy, including Bruton’s tyrosine kinase (BTK) inhibitors. Lisaftoclax marks the first Bcl-2 inhibitor to gain conditional approval and marketing authorization for CLL/SLL in China and the second globally approved Bcl-2 inhibitor.

Lisaftoclax is an orally administered small-molecule Bcl-2 selective inhibitor developed by Ascentage Pharma to treat malignancies by selectively blocking the antiapoptotic protein Bcl-2, thereby restoring the normal apoptosis process in cancer cells. Clinical trials have demonstrated its broad therapeutic potential across multiple hematologic malignancies and solid tumors, particularly in CLL/SLL, both as a standalone treatment and in combination therapies. Following olverembatinib, lisaftoclax is Ascentage Pharma’s second commercialized novel drug, highlighting the company’s strong capabilities in global clinical development and innovation.

This approval is supported by data from a pivotal registrational Phase II study (APG2575CC201), which evaluated the efficacy and safety of lisaftoclax monotherapy in patients with relapsed or refractory CLL/SLL, using overall response rate (ORR) as the primary endpoint. The study showed compelling efficacy, meeting the prespecified ORR endpoint in patients previously treated with BTK inhibitors and/or immunochemotherapy. Additionally, lisaftoclax exhibited a favorable safety profile, with no instances of tumor-lysis syndrome (TLS), manageable hematologic toxicities, and mostly grade 1-2 non-hematologic toxicities.

CLL/SLL, a hematologic malignancy caused by mature B-cell neoplasms, predominantly affects older populations, with over 100,000 new cases reported globally each year. In China, where the incidence is lower than in Western countries, CLL/SLL is rising rapidly, with a younger onset age and increased aggressiveness. While BTK inhibitors have improved outcomes as a first-line treatment, challenges such as limited deep responses, high relapse rates, and toxicities from prolonged use highlight the need for safer, more effective options.

The advent of Bcl-2 inhibitors has transformed CLL/SLL treatment by targeting the overexpressed apoptosis suppressor Bcl-2, a key factor in tumor cell survival. However, developing Bcl-2 inhibitors is challenging due to the protein’s large binding interface and its location on the mitochondrial double membrane, requiring drugs to penetrate multiple cellular layers. Prior to this approval, no Bcl-2 inhibitor was available for CLL/SLL in China, making lisaftoclax a significant advancement that addresses a critical treatment gap.

Prof. Jianyong Li from the Lymphoma Center at Jiangsu Province Hospital, the study’s principal investigator, noted, “CLL/SLL is a common hematologic malignancy in aging societies, with rising prevalence in China. Despite treatment advances, patients face drug resistance, difficult long-term management, and suboptimal response rates. Bcl-2 inhibitors, including lisaftoclax, offer a new strategy, and this approval fills a vital gap in China. As the first domestically developed Bcl-2 inhibitor, lisaftoclax’s efficacy and unique safety profile provide a meaningful new option.” In April 2025, lisaftoclax was included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies, reinforcing its role as a safe and effective treatment.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, stated, “We are encouraged by the NMPA’s recognition of lisaftoclax’s efficacy and safety, thanks to our investigators, teams, and patients. This milestone, built on over a decade of research, addresses an urgent need and advances our global innovation. We will expedite lisaftoclax’s development for various indications to benefit more patients.”

Dr. Dajun Yang, Chairman & CEO, added, “Our team’s 20 years of apoptosis research culminated in this approval, a testament to our expertise and leadership in hematology. Lisaftoclax reflects our innovation strength, and we remain committed to addressing global unmet needs with more therapeutics.”