First Patient Dosed in the Registrational Phase III Study of Olverembatinib in Treatment-Naïve Patients with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)

SUZHOU, China and ROCKVILLE, Md., Oct. 18, 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 registrational Phase III study (HQP1351AG301, NCT06051409) of olverembatinib, Ascentage Pharma’s lead drug candidate, combined with chemotherapy, versus imatinib combined with chemotherapy in treatment-naïve patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) has dosed its first patient. As a global best-in-class drug, olverembatinib holds the promise of becoming the first tyrosine kinase inhibitor (TKI) approved in China for the first-line treatment of Ph+ ALL.

This global multi-center, randomized-controlled, open-label, registrational Phase III study (HQP1351AG301) is designed to evaluate the efficacy and safety of olverembatinib combined with chemotherapy versus imatinib combined with chemotherapy in newly-diagnosed patients with Ph+ ALL.

Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival, and poor prognosis. Prior to the introduction of TKIs, a class of targeted small molecule compounds, allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving complete responses (CRs) from chemotherapy was widely adopted as a first-line treatment for patients with Ph+ ALL. However, the five-year overall survival (OS) was only less than 30% and more than 70% patients relapsed before the transplantation or simply lacked access to the surgical treatment^[1].

The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL. However, first and second-generation TKIs have known clinical limitations, including high relapse rates and disappointing long-term survival with a three to five-year OS rate of just about 50%^[2]. These limitations are primarily caused by low complete molecular responses (CMRs) and T315I kinase domain mutations, thus leaving substantial room for improvement in the treatment of Ph+ ALL. Currently, no TKI has been approved for the first-line treatment of Ph+ ALL in China and third-generation TKIs with more potent efficacy can potentially provide better prognosis to patients with Ph+ ALL by inducing a higher rate of CMRs and inhibiting the T315I mutation.

Ascentage Pharma’s novel drug candidate, olverembatinib, is an orally-administered third-generation TKI and the first and only China-approved third-generation BCR-ABL inhibitor. Currently, olverembatinib is being jointly commercialized by Ascentage Pharma and Innovent Biologics. In November 2021, Olverembatinib was approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. Previously, olverembatinib received a recommendation from the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment Hematologic Malignancies as a treatment option for patients with Ph+ ALL.

(Olverembatinib is an investigational drug that has not been approved for any indication outside the Chinese mainland)

Prof. Weili Zhao, Vice President of Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital and Director of Shanghai Institute of Hematology, commented, "Ph+ ALL used to be the most high-risk and difficult-to-treat subtype of leukemia and the introduction of TKIs has resulted in improved prognosis to patients with this condition. However, clinicians face the pressing question of which TKI offers the best efficacy and safety. We hope HQP1351AG301, a clinical study evaluating olverembatinib, a China-developed next-generation TKI, can provide an answer to those important questions."

Prof. Suning Chen, Deputy Director of the Hematology Department, the First Affiliated Hospital of Soochow University and Deputy Director of Jiangsu Institute of Hematology, noted, "Since its launch, olverembatinib showed excellent efficacy in patients with Ph+ ALL. We are very hopeful for the results from the HQP1351AG301 trial, as it is the first registrational clinical study for the first-line treatment of patients with Ph+ ALL."

Prof. Yang Shen, Deputy Director of the Hematology Department at Shanghai Jiaotong University School of Medicine Affiliated Ruijin Hospital, commented, "Olverembatinib has already been approved for the treatment of chronic myeloid leukemia in China. The HQP1351AG301 trial evaluates olverembatinib in Ph+ ALL, a potential additional indication in which olverembatinib has already showed promising therapeutic utility according to existing real-world data. We hope olverembatinib will offer a new treatment option to patients with Ph+ ALL." 

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "At present, the long-term survival rate of patients with Ph+ ALL remains disappointing, thus leaving considerable room for improvement. Multiple studies have shown that more potent third-generation TKIs can offer durable responses and a higher survival rate to patients with Ph+ ALL, yet no TKIs have been approved for the first-line setting in China. We are glad that this registrational Phase III study of olverembatinib, a TKI that could potentially become the first one approved in China for the first-line treatment of Ph+ ALL, has successfully enrolled and dosed its first patient. Moving forward, we will actively advance this clinical program and try to bring this drug to market as soon as possible for the benefit of more patients."

References

[1].  Fielding A K, Rowe JM, Richards SM, et a1. Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemo therapy in the pre imatinib era results from the International ALL Trim MRCUKALIXII/ECOG 2993. Blood, 2009,113: 4489- 4496.
[2].  Elias Jabbour et. Treatment of Adults With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia-From Intensive Chemotherapy Combinations to Chemotherapy-Free Regimens: A Review. JAMA Oncol. 2022 Sep 1;8(9):1340-1348.

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 : First Patient Dosed in the Registrational Phase III Study of Olverembatinib in Treatment-Naïve Patients with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)

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