Ascentage Pharma (NASDAQ: AAPG; HKEX: 6855), a global biopharmaceutical company headquartered in Suzhou, has received clearance from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to begin a registrational Phase III clinical trial of lisaftoclax (APG-2575) for the first-line treatment of higher-risk myelodysplastic syndrome (HR-MDS). The trial, known as GLORA-4 (NCT06641414), was originally approved by China’s Center for Drug Evaluation (CDE) in 2024, underscoring the multinational scope and accelerated pace of the program.
Lisaftoclax is a novel, orally administered Bcl-2 selective inhibitor designed to restore apoptosis in cancer cells by blocking the anti-apoptotic protein Bcl-2. Already approved in China for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lisaftoclax is now being tested in combination with azacitidine (AZA) for newly diagnosed HR-MDS patients. This trial marks the second global Phase III study of lisaftoclax to secure clearance from both the FDA and EMA, making it the only Bcl-2 inhibitor currently in late-stage development for HR-MDS worldwide.
Bridging an Unmet Clinical Need
MDS is a hematologic malignancy with age-related incidence, often diagnosed around age 70, and is associated with poor outcomes, particularly in higher-risk cases where 40–60% of patients progress to acute myeloid leukemia (AML) within five years. Current treatment options are limited. Hypomethylating agents (HMAs) remain the frontline standard but deliver modest results, with overall response rates of 30–40% and a median survival of less than six months for many HR-MDS patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), the only curative option, is feasible for less than 10% of eligible patients due to age and comorbidities.
Against this backdrop, lisaftoclax has shown encouraging results. Data presented at the 2024 American Society of Hematology (ASH) Annual Meeting and the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting reported a 75% overall response rate in treatment-naïve MDS patients when combined with AZA—well above historical benchmarks for HMAs alone. Safety outcomes were also favorable, with low rates of severe hematologic toxicities, neutropenia-related infections, and dose adjustments.
Global Collaboration
The GLORA-4 study is a randomized, double-blind, multi-region Phase III trial enrolling patients across China, the U.S., and Europe. Principal investigators include Professor Xiaojun Huang, director of the Institute of Hematology at Peking University, and Dr. Guillermo Garcia-Manero, chair of the Department of Leukemia at MD Anderson Cancer Center. Their leadership highlights the study’s dual East-West structure and reflects Ascentage’s strategy of positioning lisaftoclax as a globally competitive therapy.
Ascentage Pharma’s Chief Medical Officer, Dr. Yifan Zhai, emphasized that this study could reshape the treatment landscape for HR-MDS:
“Globally, we still lack targeted therapies for first-line treatment of higher-risk MDS, which represents a huge unmet clinical need. The clearances of the GLORA-4 study by the U.S. FDA, EMA, and China CDE pave the way for lisaftoclax to potentially become the first Bcl-2 inhibitor approved for this indication, and the first targeted therapy since the introduction of HMAs.”
China’s Role in Global Oncology Development
China’s CDE approval of the trial in 2024 enabled the country to become one of the first markets to begin enrolling patients. With China’s aging population and rising incidence of MDS, the domestic significance is substantial. At the same time, China’s inclusion as a key research hub underscores the increasing integration of Chinese biopharma innovation into the global clinical development ecosystem.
If successful, GLORA-4 could lead to the first new targeted therapy for HR-MDS in over two decades, with the potential to improve survival outcomes and quality of life for thousands of patients worldwide.