2 weeks Ago By [email protected] (MENAFN)
ROCKVILLE, Md. and SUZHOU, China, Nov. 6, 2024 /PRNewswire/ -- Ascentage Pharma (6855), a global biopharmaceutical company engaged in discovering, developing, and commercializing therapies to address global unmet medical needs primarily for malignancies, today announced that the latest results from three clinical studies of one of the company's key drug candidate, lisaftoclax (APG-2575), have been selected for presentations, including an Oral Report, at the 66th American Society of Hematology (ASH) Annual Meeting.
This is the third consecutive year in which clinical results on lisaftoclax have been selected by the ASH Annual Meeting. In 2024, results from multiple clinical and preclinical studies on four of the company's investigational drug candidates (olverembatinib, lisaftoclax, APG-2449, and APG-5918) have been selected for presentations, including two Oral Reports, at the ASH Annual Meeting. Developed by Ascentage Pharma, lisaftoclax is a novel orally available Bcl-2 inhibitor with clinical benefits for an array of hematologic malignancies and solid tumors.
At this year's ASH Annual Meeting, Ascentage Pharma will present an Oral Report featuring the latest results from a Phase I/II study of lisaftoclax in patients with relapsed/refractory multiple myeloma (R/R MM) or immunoglobulin light-chain (AL) amyloidosis. Furthermore, the latest data of lisaftoclax combinations in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and myelodysplastic syndrome (MDS) will also be released in Poster Presentations at the meeting. The ASH Annual Meeting is one of the largest gatherings of the international hematology community, aggregating the latest scientific research in the pathogenesis and clinical treatment of hematologic diseases.
The 66th ASH Annual Meeting will take place on December 7-10, 2024, local time, both online and in-person in San Diego, CA (United States). "Lisaftoclax is the first Bcl-2 inhibitor in China and the second globally that has demonstrated clinical benefits and entered pivotal registrational studies," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma .
"Currently, the drug candidate is being evaluated in four registrational Phase III studies. For the clinical results of lisaftoclax to be once again selected by the ASH meeting, it underscores the clinical benefit of this drug in hematologic malignancies. Furthermore, multiple studies of four of our investigational drug candidates have been selected for presentations at the meeting this year, highlighting Ascentage Pharma's robust capabilities in global innovation and investigational clinical development.
We are eager to share detailed data at the event. Moving forward, we will continue to accelerate our clinical development programs in efforts to bring more treatment options to patients as soon as possible." An overview of presentations featuring Ascentage Pharma's drug candidates at ASH 2024: Format Drug Candidate Abstract title Abstract# Oral Presentation Olverembatinib (HQP1351) Olverembatinib as Second-Line (2L) Therapy in Patients (pts) with Chronic Phase-Chronic Myeloid Leukemia (CP-CML) 480 Lisaftoclax (APG-2575) Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light-Chain (AL) Amyloidosis 1022 Poster Presentation Olverembatinib (HQP1351) Olverembatinib (HQP1351) Overcomes Resistance/Intolerance to Asciminib and Ponatinib in Patients (pts) with Heavily Pretreated Chronic-Phase Chronic Myeloid Leukemia (CP CML): A 1.
5-Year Follow-up Update with Comprehensive Exposure-Response (E-R) Analyses 3151 Lisaftoclax (APG-2575) Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given with Accelerated Ramp-up and then Combined with Acalabrutinib or Rituximab in Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those with Prior Exposure to Venetoclax 4614 Lisaftoclax (APG-2575) Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS) 3202 Olverembatinib + Lisaftoclax 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 1443 Olverembatinib (HQP1351) A Phase 2 Study of Olverembatinib for the Treatment of Myeloid/Lymphoid Neoplasms with FGFR1 Rearrangement 1781 Olverembatinib (HQP1351) Olverembatinib 30 Mg Versus 40 Mg Every Other Day (QOD) in Patients with Tyrosine Kinase Inhibitor (TKI) Resistant or Intolerant Chronic-Phase Chronic Myeloid Leukemia (CML-CP): A Multi-Center Propensity Score-Matched Analysis 4529 Olverembatinib (HQP1351) Combination of Olverembatinib and VP Regimen for Newly Diagnosed Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia 1449 Olverembatinib (HQP1351) Olverembatinib-Therapy in Patients with Accelerated-Phase Chronic Myeloid Leukaemia: A Multi-Centre Retrospective Study from China 1767 Olverembatinib (HQP1351) Olverembatinib-Based Therapy in Patients with Philadelphia Chromosome-Positive Acute Leukemia: A Multi-Centre Retrospective Study from China 4528 Lisaftoclax + APG-2449 APG-2449, a Novel Focal Adhesion Kinase (FAK) Inhibitor, Exhibits Antileukemic Activity and Enhances Lisaftoclax (APG-2575)-Induced Apoptosis in Acute Myeloid Leukemia (AML) 4150 APG-5918 Embryonic Ectoderm Development (EED) Inhibitor APG-5918 Demonstrates Robust Antitumor Activity in Preclinical Models of T-Cell Lymphomas (TCLs) 1415 Abstract only Olverembatinib + Lisaftoclax Olverembatinib (HQP1351) in Combination with Lisaftoclax Overcomes Venetoclax Resistance in Preclinical Model of Acute Myeloid Leukemia (AML) 5777 Abstracts on lisaftoclax selected for presentations at the 2024 ASH Annual Meeting are as follows: (for details on the abstracts featuring olverembatinib, please refer to a separate press release published at the same time) Oral Presentation Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light- Chain (AL) Amyloidosis Format: Oral Presentation Abstract #: 1022 Session: 654. Multiple Myeloma: Pharmacologic Therapies: Into the Future: New Drugs and Combinations in Multiple Myeloma Time: Monday, December 9, 2024, 4:45 PM First Author: Dr. Sikander Ailawadhi, Mayo Clinic, Jacksonville, FL Highlights: Background: Introduction: This is a multicenter, open-label Phase I/II study.
Enrolled Patients and Study Methods: Efficacy Results: Safety Results: Among 49 patients in the safety population, 34 (69.4%) reported any-grade lisaftoclax treatment-related AEs (TRAEs; ≥ 5% incidence), including neutropenia (20.4%), thrombocytopenia (6.
1%), leukopenia (10.2%), nausea (16.3%), abdominal distension (10.
2%), diarrhea (12.2%), and constipation (8.2%).
A total of 11 patients experienced grade ≥ 3 TRAEs, including neutropenia (14.3%) and febrile neutropenia (2%), and 3 patients experienced lisaftoclax-related serious AEs (1 each): febrile neutropenia, acute kidney injury, and diarrhea with electrolyte imbalance. In Arm B, 1 pt experienced a dose-limiting toxicity (prolonged QT interval).
Pharmacokinetic analyses showed no drug-drug interaction (DDI) in all patients treated with lisaftoclax at all doses in combination with other therapeutic agents used in 3 arms. Conclusions: These findings suggest that lisaftoclax improves the depth of response in patients with R/R MM or AL amyloidosis when combined with Pd or DRd. These combination therapies demonstrated a favorable safety profile with no DDIs, particularly in hematologic side effects.
Poster Presentations Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given With Accelerated Ramp-up and Then Combined With Acalabrutinib or Rituximab in Patients (pts) With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those With Prior Exposure to Venetoclax Format: Poster Presentation Abstract #: 4614 Session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster III Time: Monday, December 9, 2024; 6:00 PM - 8:00 PM First Author: Dr. Matthew Davids, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA Highlights: Background: Bcl-2 inhibition with venetoclax (ven) was a major advance in CLL treatment, but the 5-week dose ramp-up to mitigate the risk of tumor lysis syndrome (TLS) and DDIs challenge treatment optimization.
Lisaftoclax is an investigational, oral Bcl-2i with a short half-life, allowing it to be ramped-up on a daily schedule. Introduction: This poster presents updated clinical data of lisaftoclax alone or combined with acalabrutinib or rituximab in patients with treatment-naïve (TN; lisaftoclax-acalabrutinib arm), relapsed/refractory, or prior ven-treated CLL/SLL. Enrolled Patients and Study Methods: Efficacy Results: The ORR for lisaftoclax plus acalabrutinib in 87 patients was 96.
6%, and the median duration of response (DOR; 95% CI, 23-NR) and median progression-free survival (PFS; 95% CI, 34-NR) were not reached. The 12- and 18-month PFS rates were 89% and 86%, respectively. Fourteen R/R CLL ven-exposed patients received lisaftoclax plus acalabrutinib: Safety Results: Conclusions: The presented data suggest that lisaftoclax combined with acalabrutinib is effective for patients with prior ven exposure, including those with progression on ven.
In this updated analysis with longer follow-up, no DDIs or new safety findings were observed in TN or R/R CLL/SLL patients treated with lisaftoclax monotherapy or combinations. Patients with prior ven exposure continue to be accrued in order to further evaluate this promising signal. A global registrational phase III study is recruiting.
Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS) Format: Poster Presentation Abstract #: 3202 Session: 637. Myelodysplastic Syndromes: Clinical and Epidemiological: Poster II Time: Sunday, December 8, 2024, 6:00 PM - 8:00 PM First Author: Prof. Huafeng Wang, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China Highlights: Background: Hypomethylating agents (HMAs) remain the standard of care in higher-risk MDS.
However, its clinical efficacy is limited, and patients who have failed or are resistant to HMAs have a poor prognosis, leaving them in need of new therapeutic options. Introduction: Preclinical data have shown that novel investigational Bcl-2 inhibitor lisaftoclax combined with an HMA can synergistically induce apoptosis in cancer cells in AML and MDS. Reported here are the follow-up safety and efficacy data from a Phase Ib/II clinical trial evaluating lisaftoclax combined with azacitidine in adults (≥18 years) with MDS.
Enrolled Patients and Study Methods: Efficacy Results: Lisaftoclax dose reduction occurred in 4 (8.2%) patients. Neither 60-day mortality nor TLS was reported.
In 8 patients with R/R MDS, the median (range) duration of treatment (DOT) was 3.2 (1.2-9.
4) months. The overall response rate (ORR=CR[12.5%]+marrow CR[62.
5%]) was 75.0% (95% CI, 34.9-96.
8). In 40 efficacy-evaluable patients with TN MDS, the median DOT (range) was 4.5 (0.
5-12.1) months; the ORR was 77.5% (95% CI, 61.
5-89.2); and the CR rate was 25.0% per IWG 2006 criteria.
Furthermore, the ORR and CR rate in 23 patients with TN MDS treated with lisaftoclax 600 mg combined with azacitidine were 73.9% and 30.4%, respectively; because these patients had a relatively longer median DOT (6.
01 months), we conducted further analyses per IWG 2023 criteria. The composite CR rate (CR2023 = CR [52.2%] + CRL [17.
4%]) was 69.6%, and the median time to CR (range) was 2.84 (1.
1-8.7) months. Both the median progression-free survival and overall survival rates were not reached.
Safety Results: Conclusions: The clinical data support an emerging role for lisaftoclax in combination with azacitidine for treatment of patients with higher-risk TN or R/R MDS. The combination therapy was efficacious and well tolerated, resulting in no 60-day mortality, few dose modifications, and low infection rates, supporting further clinical development of this combination in patients with higher-risk MDS. * Olverembatinib is an investigational drug that has not been approved for any indication outside China; lisaftoclax (APG-2575), APG-2449 and APG-5918 are investigational drugs that have not been approved in any country and region.
About Ascentage Pharma Ascentage Pharma (6855) 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. 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, 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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