Registrational Pivotal Phase III Study of Olverembatinib for the First-Line Treatment of Patients with Ph+ ALL Approved by the CDE in China

SUZHOU, China and ROCKVILLE, Md., July 6, 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 Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has approved a registrational pivotal Phase III study of olverembatinib, Ascentage Pharma's lead drug candidate, in combination with chemotherapy (investigational arm) comparing imatinib in combination with chemotherapy (control arm) for treatment of patients with naïve 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 China-approved tyrosine kinase inhibitor (TKI) for the treatment of patients with Ph+ ALL in the first-line setting.

Accounting for 20%-30% of all ALL cases in adults, Ph+ ALL is commonly associated with a high relapse rate, short progression-free survival (PFS), 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, although first and second-generation TKIs have considerable 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 for 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. Olverembatinib was approved by the CDE of the China NMPA in November 2021 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.

"This approval for the pivotal Phase III study in newly diagnosed patients with Ph+ ALL marks a major milestone for the development of olverembatinib," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "TKIs combined with chemotherapy is a widely recognized standard treatment strategy for patients with Ph+ ALL, but no TKI has been approved for the first-line setting in this therapeutic area, thus potentially making olverembatinib the first TKI approved for the first-line treatment of Ph+ ALL in China. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will expeditiously advance the clinical development of olverembatinib in efforts to allow more patients to benefit from this novel therapeutic as soon as possible."

About Olverembatinib (HQP1351)

Developed by Ascentage Pharma with support from the National Major New Drug Discovery and Manufacturing Program in China, the orally active, third-generation TKI olverembatinib is the first and only China-approved third-generation BCR-ABL inhibitor targeting drug-resistant chronic myeloid leukemia (CML). Olverembatinib can effectively target a spectrum of BCR-ABL mutants, including the T315I mutation.

In November 2021, olverembatinib was granted a conditional approval through the Priority Review process by the China National Medical Products Administration (NMPA) for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic-phase CML (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation as confirmed by a validated diagnostic test. Subsequently, Olverembatinib was included into the China 2022 National Reimbursement Drug List (NRDL) for the approved indication. In March 2021, olverembatinib was granted a Breakthrough Therapy Designation (BTD) by the CDE for the treatment of patients with CML-CP who are resistant and/or intolerant of first- and second-generation TKIs. In July 2022, an NDA for this indication was accepted by the NMPA and subsequently granted a BTD that will support a full approval of olverembatinib.

In overseas, olverembatinib was cleared by the US FDA in July 2019 to directly enter a Phase Ib study. Since 2018, the clinical results of olverembatinib have been selected for oral presentations at the American Society of Hematology (ASH) Annual Meetings for five consecutive years, and was nominated for "Best of ASH" in 2019. To date, olverembatinib has been granted one Fast Track Designation (FTD) and four Orphan Drug Designations (ODDs) from the US Food and Drug Administration (FDA) for the treatment of CML, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and gastrointestinal stromal tumour (GIST); and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.

In July 2021, Ascentage Pharma (6855.HK) and Innovent Biologics (1801.HK) reached the agreement regarding the joint development and commercialization of olverembatinib in China.

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

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 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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