China CDE Clears Phase III Study of Lisaftoclax in High-Risk Myelodysplastic Syndrome

Ascentage Pharma, a global biopharmaceutical company based in ROCKVILLE, Md. and SUZHOU, China, has received clearance from the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) to commence a registrational Phase III study of lisaftoclax (APG-2575). Lisaftoclax, an orally administered Bcl-2 selective inhibitor, will be evaluated in combination with azacitidine (AZA) for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS). This marks the fourth registrational Phase III study for lisaftoclax, representing a significant milestone in its clinical development.

The study, known as GLORA-4, will be a multi-center, randomized, double-blind Phase III trial aimed at assessing the efficacy of lisaftoclax in combination with AZA in newly-diagnosed adult patients with higher-risk MDS. MDS is a heterogeneous myeloid clonal disease that originates from hematopoietic stem cells and is prevalent in older adults, with a median onset age of 70 years. Characterized by the abnormal growth of myeloid cells, MDS manifests through hematopoietic failure, refractory cytopenia, and a high propensity for progression to acute myeloid leukemia (AML). Approximately 10% of low-risk MDS patients and 50% of high-risk MDS patients progress to AML, facing a poor prognosis.

Currently, treatment options for MDS are limited, with demethylation agents such as AZA or decitabine being the standard first-line treatment for higher-risk patients. Studies have shown that AZA monotherapy can improve the overall survival of MDS patients compared to conventional care regimens. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for MDS, but the complex characteristics of the disease and the advanced age of patients limit the tolerability of chemotherapies and reduce the transplantation rate. Additionally, the high mortality rate associated with allo-HSCT underscores the urgent need for novel therapies and medicines with higher efficacy for higher-risk MDS patients.

Lisaftoclax, developed by Ascentage Pharma, functions by selectively inhibiting the antiapoptotic protein Bcl-2, thereby restoring the natural apoptosis process in cancer cells. The drug has shown clinical activity in treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) and has entered pivotal registrational studies. In clinical results presented at the 2023 American Society of Hematology (ASH) Annual Meeting, lisaftoclax demonstrated both clinical benefit and tolerability in higher-risk MDS patients.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, emphasized the significant unmet clinical need for MDS patients and highlighted the promising early clinical results of lisaftoclax. He expressed optimism about the approval to initiate the registrational Phase III study, indicating that it paves the way for further clinical trials and development of lisaftoclax. Dr. Zhai reiterated the company's commitment to addressing unmet clinical needs in China and globally, aiming to benefit more patients through the active advancement of lisaftoclax's clinical trials.

Ascentage Pharma is a biopharmaceutical company dedicated to discovering, developing, and commercializing innovative therapies for malignancies. The company has a robust pipeline of nine clinical-stage drug candidates, including novel Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, and candidates targeting IAP and MDM2-p53 pathways, as well as next-generation TKIs. Ascentage Pharma has conducted over 40 clinical trials across the US, Australia, Europe, and China, including 11 registrational studies.

The company's lead asset, olverembatinib, developed for drug-resistant chronic myeloid leukemia (CML), received multiple designations, including Priority Review and Breakthrough Therapy by the CDE of China NMPA. Olverembatinib has been included in the China National Reimbursement Drug List and granted Orphan Drug Designations by the US FDA and EMA of the EU.

Leveraging its strong R&D capabilities, Ascentage Pharma has established a global intellectual property portfolio and formed partnerships with leading biotechnology and pharmaceutical companies, as well as top research institutions. The company's mission is to continuously strengthen its R&D capabilities and accelerate clinical development to address unmet clinical needs worldwide.