Registrational Phase III Study of Lisaftoclax in Newly-Diagnosed Patients with Higher-Risk Myelodysplastic Syndrome Cleared by China CDE

ROCKVILLE, Md. and SUZHOU, China, Aug. 13, 2024 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing both first- and best-in-class therapies for malignancies, announced today it has been cleared by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) to initiate a registrational Phase III study of lisaftoclax (APG-2575), one of the company's key drug candidates, in combination with azacitidine (AZA) for the first-line treatment of newly-diagnosed patients with higher-risk myelodysplastic syndrome (MDS). This clears the fourth registrational Phase III study of lisaftoclax, marking another major milestone in the clinical development of the drug.

This study (GLORA-4) is a multi-center, randomized, double-blind, pivotal registrational Phase III trial to evaluate the efficacy of lisaftoclax in combination with AZA in newly-diagnosed adult patients with higher-risk MDS.

As a heterogeneous myeloid clonal disease originating from hematopoietic stem cells, MDS commonly occurs in older population with a median age of onset of 70 years and an incidence rate that increases with age.¹ MDS is characterized by the abnormal growth of myeloid cells. Its clinical manifestations include hematopoietic failure, refractory cytopenia, and the propensity for high-risk patients to progress to acute myeloid leukemia (AML). Data show that approximately 10% of low-risk patients and 50% of high-risk patients with MDS would progress to AML and thereafter face a dismal prognosis.²

At present, there are limited treatment options for patients with MDS and the treatment outcome for most patients remains relatively poor. Demethylation agents (AZA or decitabine) are the current standard first-line treatment for patients with higher-risk MDS. Studies showed that compared to conventional care regimens, monotherapy with AZA can improve the overall survival of patients with MDS.³ Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only available curative treatment for MDS. However, the complex characteristics of MDS and the old ages of patients have resulted in the intolerability of chemotherapies that limited the rate of transplantation, and the high rate of transplantation-associated mortality among patients with MDS. The low survival rate of patients with higher-risk MDS underscores an urgent unmet medical need for novel therapies and medicines that can offer higher efficacies.

Lisaftoclax is a novel, orally administered Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat the patients with malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. Lisaftoclax is expected to be the first Bcl-2 inhibitor for which an NDA will be filed for chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) in China and the second anywhere globally that has demonstrated clinical activity for the treatment of patients with CLL and entered pivotal registrational studies. In published clinical results released at the 2023 American Society of Hematology (ASH) Annual Meeting, the drug candidate lisaftoclax has demonstrated clinical benefit and tolerability in patients with higher-risk MDS.⁴

"There is considerable unmet clinical need for patients with MDS. Lisaftoclax, a Bcl-2 inhibitor, has already shown promising clinical benefit and tolerability in early studies in patients with MDS," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by this approval for initiation of the registrational Phase III study in the first-line treatment of patients with higher-risk MDS, as it clears the way for the fourth registrational Phase III study of lisaftoclax. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will actively press ahead with the clinical trials of lisaftoclax for the benefit of more patients."

*Lisaftoclax is an investigational drug that has not been approved in any country or region.

References:

1. Fenaux P, Haase D, Santini V, et al. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021 Feb;32(2):142-156. doi: 10.1016/j.annonc.2020.11.002.
2. NCCN Guidelines® Version 1.2023 on Myelodysplastic Syndromes
3. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8.
4. Wang H, Wei X, Jiang Q, et al. Safety and Efficacy of Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor (BCL-2i), in Relapsed or Refractory (R/R) or Treatment-Naïve (TN) Patients (Pts) with Acute Myeloid leukemia (AML), Myelodysplastic Syndrome (MDS), or Other Myeloid Neoplasms. Blood (2023) 142 (Supplement 1): 2925. https://doi.org/10.1182/blood-2023-188489 

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing both first-in-class and best-in-class therapies to address global unmet medical needs primarily in malignancies. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

The company has built a pipeline of 9 clinical-stage drug candidates, including novel, highly potent Bcl-2 and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation TKIs. Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 registrational studies (completed/ ongoing/planned).

Olverembatinib, the company's first lead asset developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product in China, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted Orphan Drug Designations (ODDs) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU.

To date, Ascentage Pharma has obtained a total of 16 ODDs from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies such as Takeda, AstraZeneca, Merck, Pfizer and Innovent; and research and development relationships with leading research institutions such as Dana-Farber Cancer Institute, Mayo Clinic, MD Anderson Cancer Center, National Cancer Institute and the University of Michigan.

The company has built a talented team with a wealth of global experience in the discovery and development of innovative drugs and fully functional commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

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source: Ascentage Pharma