Global Registrational Phase III Study of Bcl-2 Inhibitor Lisaftoclax in Treatment-Naïve Patients with CLL/SLL Approved by the China CDE

ROCKVILLE, Md. and SUZHOU, China, Oct. 13, 2023 /PRNewswire/ — Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved a global pivotal registrational Phase III study designed to evaluate a key drug candidate in Ascentage Pharma’s pipeline, Bcl-2 inhibitor APG-2575 (Lisaftoclax), in combination with the Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib, versus immunochemotherapy in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), aiming to validate the combination regimen as a first-line treatment for CLL/SLL. This approval marks another major milestone in the clinical development of the drug candidate following the clearance from the US Food and Drug Administration (FDA) in August 2023 for the global registrational Phase III study in patients with CLL/SLL who have received prior therapies.

This global multi-center, randomized-controlled, open-label, pivotal Phase III confirmatory trial (APG2575CC301) is designed to evaluate the efficacy and safety of APG-2575 (lisaftoclax) combined with acalabrutinib versus immunochemotherapy in treatment-naïve patients with CLL/SLL.

CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. It primarily affects older populations and is among the most common leukemia subtypes in adults, accounting for a quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses reported globally each year¹. In China, CLL/SLL is occurring at a rapidly rising incidence rate, with a younger age of onset and higher aggressiveness², thus posing a serious threat to public health in the country. Advancements in basic research and targeted therapies have brought significant survival benefit to patients with CLL/SLL. However, CLL/SLL still presents major clinical challenges and urgent medical needs for new treatment options that can offer both efficacy and safety.

APG-2575 (Lisaftoclax) is a novel, orally administered small-molecule 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. With strong global best-in-class potential, lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal registrational study. At present, lisaftoclax is being evaluated in multiple clinical studies across the world and more than 300 patients with CLL/SLL have already been treated with the drug either as a monotherapy or in combinations. Interim results suggest that lisaftoclax offers potent efficacy to patients with CLL/SLL and has the potential as a safe, efficacious, and convenient treatment option.

The preliminary results from a global Phase II study have already showed therapeutic potential of lisaftoclax in combination with acalabrutinib, with an objective response rate (ORR) of 98% in patients with relapsed/refractory (R/R) CLL/SLL, an ORR of 100% in treatment-naïve patients with CLL/SLL, and an excellent safety profile that is on par with that of lisaftoclax monotherapy. In the study, lisaftoclax was initiated on a daily ramp-up that simplified the dosing schedule and allowed patients receive the treatment dose more quickly³. Moreover, the study adopted a dosing regimen that was improved on that of existing Bcl-2 inhibitor plus BTK inhibitor combinations as it eliminated the lead-in for the BTK inhibitor, thus allowed patients to begin receiving the combination therapy more quickly. Those results were being released as an Oral Presentation at the 2022 American Society of Hematology (ASH) Annual Meeting.

"In earlier studies, lisaftoclax combined with acalabrutinib has already demonstrated impressive efficacy and safety, validating the combination regimen’s therapeutic potential and its promise as a patient-centric treatment strategy," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "We are very encouraged by this approval for the global registrational Phase III study of lisaftoclax combined with acalabrutinib. In terms of the dose ramp-up schedule for the Bcl-2 inhibitor and no lead-in of the BTK inhibitor, this trial adopts an innovative and optimized dosing regimen that is more convenient and allows for a faster onset of actions compared to studies of similar combinations. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will vigorously advance those clinical programs of lisaftoclax to expedite the drug’s journey to market for the benefit of more patients."

References

1. Yao, Y., Lin, X., Li, F. et al. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. BioMed Eng OnLine 21, 4 (2022). https://doi.org/10.1186/s12938-021-00973-6

2. 刘澎. 复旦大学附属中山医院慢性淋巴细胞白细胞/小淋巴细胞淋巴瘤诊疗规范（v1.2018）[J].中国临床医学, 2018, 25(1).

3. Davids M, Chanan-Khan A, Mudenda B, et al. Lisaftoclax (APG-2575) Safety and Activity As Monotherapy or Combined with Acalabrutinib or Rituximab in Patients (pts) with Treatment-Naïve, Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (R/R CLL/SLL): Initial Data from a Phase 2 Global Study. Blood (2022) 140 (Supplement 1): 2326–2328.

4. Ailawadhi S, Chen Z, Huang B, Paulus A, Collins MC, Fu LT, Li M, Ahmad M, Men L, Wang H, Davids MS, Liang E, Mekala DJ, He Z, Lasica M, Yannakou CK, Parrondo R, Glass L, Yang D, Chanan-Khan A, Zhai Y. Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial. Clin Cancer Res. 2023 Jul 5;29(13):2385-2393.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. 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.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical 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 tyrosine kinase inhibitors (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 is conducting more than 40 Phase I/II clinical trials in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases.

Olverembatinib, the company’s core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company’s first approved product, 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 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) 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, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations 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 with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class 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.

Forward-Looking Statements

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Source : Global Registrational Phase III Study of Bcl-2 Inhibitor Lisaftoclax in Treatment-Naïve Patients with CLL/SLL Approved by the China CDE

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