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Highlights

  • FDA and EMA cleared GLORA-4 Phase III to study lisaftoclax plus azacitidine.
  • Earlier trials reported a 75% overall response rate versus current standard therapies.
  • Simultaneous multi-region enrollment in China, U.S., and Europe accelerates data collection.

Ascentage Pharma announced regulatory clearances from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to initiate GLORA-4, a global Phase III registrational study of lisaftoclax in combination with azacitidine for first-line treatment of higher-risk myelodysplastic syndrome (HR-MDS). The randomized, double-blind, multi-center trial will enroll patients across China, the United States, and Europe, positioning the program to generate pivotal data across geographically diverse patient populations.

Lisaftoclax is a proprietary Bcl-2 inhibitor and, according to the company, is currently the only Bcl-2 inhibitor in Phase III development for HR-MDS worldwide. Earlier clinical data cited by Ascentage reported an overall response rate (ORR) of approximately 75% in earlier studies — a figure materially higher than response rates typically associated with existing hypomethylating agents. Those early results underpin the rationale for a registrational trial and explain the simultaneous filings with major regulators.

The GLORA-4 design and the synchronized regulatory clearances aim to streamline the pathway toward potential market authorization if the trial meets its endpoints. Conducting a multi-region trial may help validate efficacy and safety across heterogeneous patient groups and should allow for more generalisable regulatory submissions. Ascentage notes a favorable safety profile in prior work, with a low incidence of severe toxicities, and the company already holds approval in China for lisaftoclax in a different indication (CLL/SLL), which may inform manufacturing and post-marketing strategies.