Live from ASH 2023 | Ascentage Pharma Releases Encouraging Long-Term Data of Bcl-2 Inhibitor Lisaftoclax in R/R CLL, Including an ORR of 73.3%

SUZHOU, China and ROCKVILLE, Md., Dec. 10, 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 it has released the latest efficacy and safety data of lisaftoclax (APG-2575), one of the company's key drug candidates, in patients with heavily pretreated chronic lymphocytic leukemia (CLL), in a Poster Presentation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States.

The ASH Annual Meeting is one of the largest gatherings of the international hematology community, bringing together the most cutting-edge scientific research and latest data of investigational therapies that represent leading scientific and clinical advances in the global hematology field. Garnering growing interest from the global research community, multiple studies of Ascentage Pharma's key drug candidates (lisaftoclax and olverembatinib) have been selected for presentations at this year's ASH Annual Meeting, including two Oral Presentations.

These data in patients with R/R CLL reaffirmed the potential clinical benefit and tolerability of lisaftoclax. Results showed an overall response rate (ORR) of 73.3%; a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 24.4%; and a positive correlation between CR/CRi rate and dose levels. In addition, the study observed a low incidence of tumor lysis syndrome (TLS) that is comparable to the results of earlier studies.

Prof. Keshu Zhou, MD, at Henan Cancer Hospital and the presenter of this report, commented, "Our report this year has focused on the efficacy, particularly deep responses including the CR/CRi rate and measurable residual disease (MRD) negativity of Chinese patients with R/R CLL who were treated with lisaftoclax monotherapy. Having been treated with a wide spectrum of doses that ranged from 100 to 800 mg, these patients showed a CR/CRi rate of 24.4%. While in long-term follow-up, the study observed a 30-month overall survival (OS) rate of 86.3% that indicated the drug's potential in bringing long-term survival benefit to patients with CLL." 

Prof. Jianyong Li, MD, at Jiangsu Province Hospital and the principal investigator of the study, noted, "In a series of Phase Ib/II studies carried out in China and overseas, lisaftoclax has demonstrated its strong therapeutic potential, while results from long-term follow-up reaffirmed the high response rate, long-term safety, and long-term survival benefit of lisaftoclax. In the field of CLL, lisaftoclax has made considerable strides towards confirmatory trials. We hope that this Bcl-2 inhibitor will soon have these results validated in larger samples of the broad CLL population and eventually be approved for wide clinical adoption."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "Lisaftoclax is the first Bcl-2 inhibitor that demonstrated clear efficacy in China and the second globally. At this year's ASH Annual Meeting, we presented encouraging data of lisaftoclax in patients with CLL that reaffirmed the drug's promising clinical benefit, favorable tolerability, and strong global best-in-class potential. Remaining committed to the mission of the addressing unmet clinical needs in China and around the world, we will expedite our clinical development programs to bring safe and effective therapies to patients in need."

Highlights of the study presented at ASH 2023:

Updated Efficacy and Safety Results of Lisaftoclax (APG-2575) in Patients (pts) with Heavily Pretreated Chronic Lymphocytic Leukemia (CLL): Pooled Analyses of Two Clinical Trials

Format: Poster Presentation
Abstract: #1900
Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster I
Time: Saturday, December 9, 2023; 5:30 PM - 7:30 PM (Pacific Time) / Sunday, December 10, 2023; 9:30 AM – 11:30 AM (Beijing Time)
Highlights:
Background: Lisaftoclax is a novel selective Bcl-2 inhibitor that has demonstrated antileukemic activity and favorable tolerability in patients with CLL. This poster reported updated data from 14-month follow-up in two Phase Ib/II studies (APG-2575-CN001 [NCT03913949] and APG-2575-CC101 [NCT04494503]) of lisaftoclax in patients with CLL.

Methods: In the 2 studies, lisaftoclax was administered orally once daily in 28-day cycles, in 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg dose cohorts. Under close monitoring for prevention and early detection of TLS, patients were treated (with a daily dose ramp-up schedule) until disease progression, intolerable toxicity, or death.

Patients: As of April 27, 2023, a total of 47 patients with CLL were enrolled. The median (range) age was 58 (34-80) years. At enrollment, 53.2% of patients were in Rai stage III/IV, and 48.9% of patients were in Binet stage C. 44.7% of patients had received ≥3 lines of treatment; 66.0% of patients had received ≥2 lines of treatment; 23.4% of patients were previously treated with Bruton tyrosine kinase inhibitors (BTKis); and 55.3% were previously treated with a CD20 monoclonal antibody.

Efficacy results: In patients with CLL, the ORR and CR/CRi were 73.3% (33/45) and 24.4% (11/45), respectively, and the CR/CRi rate exhibited an upward trend with increases in dose levels. Among patients who were tested for MRD in peripheral blood, 38.9% (7/18) achieved the MRD-negative status. Among patients who were tested for MRD in bone marrow, 66.7% (4/6) were MRD-negative. The median time (range) to the first response was 2.07 (1.94-3.94) months, the median progression-free survival (PFS) was 18.53 (95% CI, 9.13-24.05) months, and the rate of OS at month 30 was 86.3% (95% CI, 66.1%-94.9%).

Safety results: In total, 76.6% (36) of patients experienced grade ≥3 adverse events (AEs); 27.7% (13) experienced serious AEs (SAEs). The incidence of treatment-emergent AEs (TEAEs) was not dose-dependent. Treatment-related adverse events (TRAEs) were observed in 95.7% (45) of patients, of whom 68.1% (32) experienced grade ≥3 TRAEs and 14.9% (7) experienced SAEs. One case of TLS was reported. 68.1% (32) of patients discontinued the study because of disease progression (51.1%), patient withdrawal (6.4%), AEs (2.1%), investigator's decision (2.1%), poor compliance (2.1%), protocol deviation (2.1%), and other reasons (2.1%).

Conclusions: Lisaftoclax demonstrated favorable tolerability and significant efficacy in patients with R/R CLL, and the CR/CRi rate was positively correlated with escalating dose levels.

* Lisaftoclax (APG-2575) is an investigational drug that has not been approved in any country and region.

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.

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SOURCE Ascentage Pharma