ROCKVILLE, MD, the United States, and SUZHOU, China, December 10, 2024—Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that it has released the safety and efficacy data of the company’s novel drug candidate, olverembatinib (HQP1351), in combination the company’s investigational novel Bcl-2 inhibitor, lisaftoclax (APG-2575), in children and adolescents with relapsed/refractory Philadelphia chromosome–positive acute lymphoblastic leukemia (R/R Ph+ ALL), in a Poster Presentation at the 66th American Society of Hematology (ASH) Annual Meeting, taking place in San Diego, CA, the United States. This poster, named for the Abstract Achievement Award at ASH 2024, features the first batch of clinical data on the combination of Ascentage Pharma’s two key drug candidates.
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, results from multiple clinical and preclinical studies on four of Ascentage Pharma’s drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at this year’s ASH Annual Meeting.
This study in children and adolescents with R/R Ph+ ALL provides the preliminary evidence revealing the favorable efficacy and safety of olverembatinib in combination with lisaftoclax. These data showed a complete response (CR) rate of 83.3% and measurable residual disease (MRD) negativity rate of 71.4% in patients who were treated with the combination regimen without chemotherapy or immunotherapy.
As the first approved third-generation BCR-ABL inhibitor in China, olverembatinib has already been approved for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant CP-CML or accelerated-phase (AP-) CML harboring the T315I mutation; and adult patients with CP-CML resistant to and/or intolerant of first- and second-generation TKIs. Olverembatinib is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics.
Prof. Xiaofan Zhu, the principal investigator of this study from the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, commented, “In recent years, we have seen considerable progress in the treatment of pediatric patients with hematologic diseases in China. However, due to a unique disease profile, the prognosis of patients with Ph+ ALL remains relatively poor, thus leaving much to be explored in the treatment of R/R Ph+ ALL. These preliminary clinical data show that the third-generation BCR-ABL1 inhibitor, olverembatinib, in combination with the novel Bcl-2 inhibitor, lisaftoclax, without chemotherapy or immunotherapy, has demonstrated a compelling CR rate, MRD negativity rate, and favorable tolerability in pediatric patients. We look forward to determining the optimal doses and dosing regimens for the combination therapy as we search for more safe and effective treatment options for pediatric patients with R/R Ph+ ALL.”
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, “This regimen, the first combination between olverembatinib and lisaftoclax, two of Ascentage Pharma’s key drug candidates, has demonstrated encouraging clinical benefit, favorable safety, rapid onset of actions, as well as higher and deeper responses in absence of chemotherapy or immunotherapy. This suggests that the combination regimen may offer a new treatment option and open an era of chemotherapy-free management for patients with Ph+ ALL. Fulfilling our founding mission of addressing unmet clinical needs in China and around the world, we will expedite the global clinical development of our key drug candidates to bring more safe and effective therapies to patients as soon as possible.”
Highlights of the data this study reported at ASH 2024 are as below:
Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph+ ALL): First Report from a Phase 1 Study
Format: Poster Presentation
Abstract#: 1443
Session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster I
Highlights:
Background: Olverembatinib, a novel third-generation TKI, is well tolerated and exerts strong and durable antileukemic activity in patients with heavily pretreated CP-CML with or without the T315I mutation. Investigational lisaftoclax, a novel Bcl-2 inhibitor, has shown clinical antitumor benefits in patients with multiple hematologic malignancies. Currently, there are no effective treatment options available for pediatric patients with R/R Ph+ ALL.
Introduction: This study was designed to explore the safety, efficacy, and pharmacokinetic (PK) profile of olverembatinib alone or combined with lisaftoclax in children and adolescents with R/R Ph+ ALL.
Enrolled Patients and Study Methods:
Efficacy Results: Among 6 patients evaluable for morphologic responses, 2 patients achieved CRs with incomplete count recovery (CRis), 2 achieved partial responses (PRs) at the end of olverembatinib monotherapy (EOM), resulting in an ORR (CR+CRi) of 33.3%; and 5 (83.3%) patients achieved CRs at the end of olverembatinib and lisaftoclax combination course (EOC). In the 7 patients who were evaluable for molecular responses, 5 (71.4%) achieved MRD negativity, of which 1 was at EOM and 4 at EOC.
Safety Results:
Conclusions: These preliminary data showed that olverembatinib in combination with lisaftoclax appears to be a safe and effective regimen in pediatric patients with R/R Ph+ ALL. This regimen resulted in a promising CR rate of 83.3% and MRD negativity rate of 71.4% without intensive chemotherapy or immunotherapy. The study is currently in the dose-expansion phase.
* Olverembatinib is an investigational drug that has not been approved for any indication outside China; 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 global, integrated biopharmaceutical company engaged in discovering, developing and commercializing 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 rich pipeline of innovative drug candidates that includes 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 13 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, 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.
Forward-Looking Statements
The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions and expectations or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions and expectations may alter in light of future development.