Ascentage Pharma Receives FDA and EMA Clearance for Global Phase III Trial of Olverembatinib in Philadelphia Chromosome-Positive ALL
核心洞察
Ascentage Pharma (搜索) has received clearance from the US FDA and European Medicines Agency (搜索) to conduct the POLARIS-1 global registrational Phase III study of olverembatinib combined with chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (搜索) patients.
Early data from the POLARIS-1 study shows approximately 65% minimal residual disease negativity rate and molecular complete response rate at the end of three treatment cycles, significantly improving upon efficacy reported for other drugs in the same class.
Philadelphia chromosome-positive ALL accounts for 20-30% of all adult ALL cases and is associated with high relapse rates and poor prognosis, with historical five-year overall survival rates of less than 20% before tyrosine kinase inhibitor introduction.
Ascentage Pharma (搜索) Group International has achieved a significant regulatory milestone with clearances from both the US Food and Drug Administration (搜索) and the European Medicines Agency (搜索) to conduct a global registrational Phase III study of olverembatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia (搜索) (Ph+ ALL (搜索)). The POLARIS-1 trial (NCT06051409) represents the second global registrational Phase III study of olverembatinib cleared by US and European regulators, positioning the company to accelerate the drug's path to worldwide registration.
Study Design and Early Efficacy Signals
The POLARIS-1 trial is designed as a global, multicenter, randomized controlled, open-label Phase III study evaluating the efficacy and safety of olverembatinib in combination with chemotherapy in newly diagnosed Ph+ ALL (搜索) patients. The study is simultaneously enrolling patients across multiple countries to expedite global development, particularly in US and European markets.
Preliminary data from the POLARIS-1 study, set to be presented at the 2025 American Society of Hematology Annual Meeting, demonstrates promising efficacy signals. Among treatment-naïve Ph+ ALL (搜索) patients receiving olverembatinib combined with low-intensity chemotherapy, both the minimal residual disease (MRD) negativity rate and molecular MRD-negative complete response rate reached approximately 65% at the end of three treatment cycles. According to the company, this represents a significant improvement over efficacy reported for other drugs in the same therapeutic class.
The combination regimen showed particular clinical benefit in high-risk patient subtypes, including those harboring the IKZF1plus mutation. Additionally, the treatment demonstrated a favorable safety profile with low incidence of adverse events that were mostly manageable.
Addressing Critical Unmet Medical Need
Ph+ ALL (搜索) represents a substantial clinical challenge, accounting for 20-30% of all adult ALL cases. The disease is characterized by disproportionately high incidence in elderly populations, elevated relapse rates, shortened disease-free survival, and poor overall prognosis. Historical treatment outcomes underscore the severity of this condition: prior to the introduction of tyrosine kinase inhibitors, chemotherapy-only treatment delivered five-year overall survival rates of less than 20%.
While the clinical adoption of TKIs has established a new treatment paradigm for Ph+ ALL (搜索) patients, first- and second-generation TKIs maintain considerable limitations in treating this aggressive hematologic malignancy.
Third-Generation TKI Innovation
Olverembatinib represents a novel third-generation tyrosine kinase inhibitor and stands as the first China-approved third-generation BCR-ABL (搜索) inhibitor. The orally administered compound is currently being jointly commercialized in China by Ascentage Pharma (搜索) and Innovent Biologics (搜索) across multiple chronic myeloid leukemia (搜索) indications, all of which are covered by the China National Reimbursement Drug List.
For Ph+ ALL (搜索) treatment specifically, olverembatinib has received consecutive recommendations in the Chinese Society of Clinical Oncology Guidelines for the Diagnosis and Treatment of Hematologic Malignancies and earned Breakthrough Therapy Designation from the China Center for Drug Evaluation.
Global Development Strategy
Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma (搜索), emphasized the significance of the regulatory clearances: "Clearances from the U.S. FDA and the EMA for this global registrational Phase III study mark a significant step forward in the global development of olverembatinib in Ph+ ALL (搜索). Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will press ahead with the clinical development of olverembatinib in Ph+ ALL and strive to bring a new treatment option to patients around the world as soon as possible."
The company's global expansion strategy includes a significant partnership component. In June 2024, Ascentage signed an exclusive option agreement with Takeda (搜索) for olverembatinib. Should Takeda exercise this option, the pharmaceutical giant would license global rights to develop and commercialize olverembatinib in all territories outside of mainland China, Hong Kong, Macau, and Taiwan.
Broader Pipeline Development
Beyond the POLARIS-1 study, Ascentage Pharma (搜索) is conducting multiple global registrational Phase III trials for olverembatinib, including the FDA-cleared POLARIS-2 trial for chronic myeloid leukemia (搜索) and studies in SDH-deficient gastrointestinal stromal tumor patients. The company's broader oncology portfolio includes lisaftoclax, a novel Bcl-2 (搜索) inhibitor approved in China for chronic lymphocytic leukemia (搜索)/small lymphocytic lymphoma (搜索) treatment, with four ongoing global registrational Phase III trials across various hematologic malignancies.