On January 10, 2024 Ascentage Pharma (6855.HK), a commercial stage global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, reported that Dr. Dajun Yang, the company’s Chairman and CEO, gave a speech at the 42nd Annual J.P. Morgan Healthcare Conference (Press release, Ascentage Pharma, JAN 10, 2024, View Source [SID1234639190]). In the presentation, Dr. Yang provided an update on Ascentage Pharma’s recent major milestones and the formidable competitiveness the company has built in the field of hematologic malignancies, all achieved under its patient-centric global innovation strategy.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
Approvals for multiple global registrational Phase III trials mark new milestones in global innovation
As an innovative drug company pursuing a patient-centric global innovation strategy, Ascentage Pharma has achieved major milestones with its global expansion in 2023, including approvals for multiple global registrational Phase III studies of olverembatinib (HQP1351) and lisaftoclax (APG-2575), two of the company’s key drug candidates.
In-house developed by Ascentage Pharma, the novel drug olverembatinib is the first and only China-approved third-generation BCR-ABL inhibitor that filled a major treatment gap for Chinese patients with drug-resistant CML. In July 2023, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) approved a global registrational pivotal Phase III study of olverembatinib, Ascentage Pharma’s lead drug candidate, in combination with chemotherapy versus imatinib in combination with chemotherapy for the treatment of newly diagnosed patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This approval marks a major milestone that could potentially pave the way for olverembatinib to become the first tyrosine kinase inhibitor (TKI) approved in China for the treatment of patients with Ph+ ALL in the first-line setting.
In August 2023, the US Food and Drug Administration (FDA) cleared a global registrational pivotal Phase III study of the Bcl-2 inhibitor lisaftoclax, another one of Ascentage Pharma’s key drug candidates, in previously treated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This regulatory clearance marked a major step in the global clinical development of lisaftoclax as it can potentially accelerate the drug’s journey to market as the world’s second approved Bcl-2 inhibitor, further validating the company’s capabilities in innovation and global clinical development.
Two months after that, lisaftoclax achieved another breakthrough with a clinical trial approval by the China CDE for a global registrational pivotal Phase III study of lisaftoclax combined with the Bruton’s tyrosine kinase (BTK) inhibitor acalabrutinib, versus immunochemotherapy for the first-line treatment of naïve patients with CLL/SLL.
Olverembatinib approved for a new indication while having its global first-in-class potential further validated
Ever since launching olverembatinib, Ascentage Pharma has stepped up the commercialization of the drug and achieved a range of breakthroughs. In January 2023, as a frontrunner among National Major New Drug Development designated drugs in China, olverembatinib was included into the China 2022 National Reimbursement Drug List (NRDL), thus saw its accessibility and affordability drastically improved.
In November 2023, the NMPA approved a new indication of olverembatinib for the treatment of adult patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant of first-and second-generation TKIs, allowing a broader population of patients with CML to benefit from the drug.
At the recently concluded 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, eleven abstracts on olverembatinib were selected for presentations, including two Oral Presentations, making 2023 the sixth consecutive year in which data of olverembatinib were selected for Oral Presentations at the meeting. This is another indication of the strong global best-in-class potential of olverembatinib.
Data from the Chinese study of olverembatinib (HQP1351CC203), selected for an Oral Presentation at ASH (Free ASH Whitepaper) 2023, showed that in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs, the olverembatinib arm achieved statistically significant improvement in event-free survival (EFS) compared to the control arm that was treated with the best available therapy (BAT), thus meeting the primary endpoint of the study with markedly improved prognosis for patients with CML in the olverembatinib arm, compared to those in the control arm.
Meanwhile, results from the US study of olverembatinib were equally encouraging. After releasing preliminary results of the US study in an Oral Report at the ASH (Free ASH Whitepaper) Annual Meeting in 2022, at ASH (Free ASH Whitepaper) 2023, Ascentage Pharma presented updated data from a larger patient sample that showed the favorable clinical benefit and tolerability of olverembatinib, as a monotherapy and in combinations, in heavily pretreated patients with CML and Ph+ ALL, particularly those who have failed prior treatment with the third-generation TKI ponatinib or the allosteric STAMP inhibitor asciminib. These results suggest that olverembatinib has global potential as an effective new therapy for patients with CML or Ph+ ALL.
The company is extensively exploring and validating olverembatinib’s therapeutic potential in indications other than CML, and the drug has shown particularly promising utility for the treatment of Ph+ ALL. Results from multiple studies evaluating olverembatinib in patients with Ph+ ALL were presented at ASH (Free ASH Whitepaper) 2023, including an Oral Presentation featuring a study that showed encouraging clinical benefit and favorable tolerability of olverembatinib, a potent third-generation TKI, combined with reduced-intensity chemotherapy in patients with Ph+ ALL, indicating the regimen has the potential of ushering in an era of chemotherapy-free treatment for Ph+ ALL.
While solidifying its presence and competitiveness in hematologic malignancies, Ascentage Pharma has also expeditiously advanced its clinical development of olverembatinib for the treatment of gastrointestinal stromal tumor (GIST). In 2023, the second year in which clinical results of olverembatinib in patients with GIST were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma released data that showed encouraging clinical benefit and favorable safety of olverembatinib in patients with TKI-resistant succinate dehydrogenase (SDH)-deficient GIST.
Bcl-2 inhibitor lisaftoclax showed promising clinical benefit for patients with CLL and strong therapeutic potential in AML and MM
Also during his speech, Dr. Yang reviewed the recent progress in the development of lisaftoclax, alluding to key data released at ASH (Free ASH Whitepaper) 2023.
As the first Bcl-2 inhibitor that has entered registrational pivotal trials in China and the second globally, lisaftoclax is a novel therapeutic with global best-in-class potential.
At ASH (Free ASH Whitepaper) 2023, Ascentage Pharma released results from three studies of lisaftoclax, including one study in patients with relapsed/refractory (R/R) CLL that 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 patients who received lisaftoclax. In addition, the study observed a low incidence of tumor lysis syndrome (TLS) that is comparable to the results of earlier studies. While in long-term follow-up, the study observed a 30-month overall survival (OS) rate of 86.3% that indicated the drug’s high response rates, safety for long-term use, and potential in bringing durable survival benefit to patients with CLL.
In addition, Ascentage Pharma released the first dataset of lisaftoclax in patients with multiple myeloma (MM) and acute myeloid leukemia (AML) at ASH (Free ASH Whitepaper) 2023. These data revealed strong therapeutic potential and provide a solid foundation for the continued development of lisaftoclax in indications outside CLL. Dr. Yang also mentioned in his speech that a registrational Phase III study of lisaftoclax in AML has already been approved by the China CDE and is being initiated.
Accelerating global innovation to achieve enhanced global competitiveness
Under its overarching global innovation strategy, Ascentage Pharma has built a rich pipeline composed of highly promising drug candidates with first-in-class and/or best-in-class potentials, and is conducting more than 40 clinical studies in China, the US, Australia, Europe, and Canada. The company’s innovative and clinical development capabilities have received growing recognition from the global research community as the clinical data on a number of its drug candidates were frequently showcased at major international congresses.
In his talk, Dr. Yang outlined a series of potential catalysts for 2024, including the FDA clearance for the registrational Phase III study of olverembatinib, NDA submissions for lisaftoclax, rapid progress with multiple global registrational Phase III studies, and the NRDL inclusion of olverembatinib’s new indication.
"It is my great pleasure to attend the annual J.P. Morgan Healthcare Conference this year and have the opportunity to provide an update on the key progress we delivered in 2023," said Dr. Dajun Yang. "In the past year, we received clearance for multiple global registrational Phase III studies, taking major steps forward in our global expansion; we continuously expanded the target indications of our core drug candidates and further solidified our leadership position in the arena of hematologic malignancies. Moving forward, we will continue to execute our global innovation strategies, accelerate our global registrational Phase III studies, and make further strides fulfilling our mission of addressing unmet clinical needs in China and around the world for the benefit of more patients."