Lisaftoclax Secures Approval in China for Relapsed CLL/SLL Treatment

On July 10, 2025, China’s National Medical Products Administration (NMPA) granted approval for lisaftoclax (APG-2575), marking a significant milestone for the treatment of adult patients suffering from chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have undergone at least one prior systemic therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor. This approval makes lisaftoclax the first BCL-2 inhibitor authorized for use in this patient population in China and the second of its kind approved worldwide.

The pivotal phase 2 trial (APG2575CC201; NCT05147467) that underpinned the NMPA’s decision demonstrated that lisaftoclax achieved its primary endpoint, showing a substantial overall response rate (ORR) in patients with relapsed/refractory CLL/SLL who had previously been treated with BTK inhibitors and/or chemoimmunotherapy. Importantly, the trial revealed a favorable safety profile, with no reported cases of tumor lysis syndrome and manageable hematologic and non-hematologic toxicities, as stated by Dr. Jianyong Li, a leading expert in hematologic malignancies at the Lymphoma Center of Jiangsu Province Hospital in China.

"This approval for the next-generation BCL-2 inhibitor lisaftoclax represents a timely response to the urgent unmet medical need of this patient population, effectively filling the void for BCL-2 inhibitors in CLL/SLL in China," Dr. Li remarked in a press release.

Lisaftoclax is a novel, orally administered small-molecule agent that selectively targets the BCL-2 protein, a key player in the regulation of apoptosis in cancer cells. By inhibiting this protein, the drug seeks to restore the natural death process in malignant cells, which is often disrupted in cancers like CLL and SLL.

The clinical trial was structured as a single-arm, open-label, multicenter study that involved adult patients whose CLL/SLL had progressed after or who were intolerant to previous treatments, including chemoimmunotherapy and BTK inhibitors. Participants were required to have a life expectancy of at least 12 weeks and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. They received daily doses of 600 mg of oral lisaftoclax in 28-day cycles. Alongside ORR, secondary endpoints of the study included progression-free survival, overall survival, and safety assessments, among others.

In April 2025, recognizing its groundbreaking clinical efficacy and safety profile, lisaftoclax was incorporated into the 2025 guidelines of the Chinese Society of Clinical Oncology for the diagnosis and treatment of lymphoid malignancies. Dr. Li noted, "The approval and guideline recommendations validate the drug as a safe and efficacious new treatment option, underscoring a significant advancement in precision therapy for hematologic malignancies in China."

Currently, lisaftoclax is under investigation in four global phase 3 studies: GLORA (NCT06104566), GLORA-2 (NCT06319456), GLORA-3 (NCT06389292), and GLORA-4 (NCT06641414). These trials are examining the drug in various combination therapies for patients with CLL/SLL and other hematologic malignancies, further highlighting its potential to reshape treatment paradigms.

Ascentage Pharma, the developer of lisaftoclax, emphasized its commitment to addressing unmet clinical needs both in China and globally. Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma, stated, "This approval for lisaftoclax is a culmination of over 20 years of dedicated research in the field of apoptosis and showcases our strength in drug development. We aspire to bring more innovative therapeutics to patients worldwide."

The approval of lisaftoclax not only expands the arsenal of treatment options available for CLL/SLL but also signifies a broader trend toward precision medicine in oncology, focusing on tailored therapies that improve outcomes for patients with challenging malignancies. The ongoing studies will provide further insights into the drug's efficacy and safety, potentially leading to its broader adoption in clinical practice.