ASCENTAGE PHARMA-B (06855) announced that its self-developed Class 1 innovative drug, olverembatinib (brand name: Nerlynx®), has received approval from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to initiate a global Phase III registration study (POLARIS-1, NCT06051409). The study will evaluate the efficacy and safety of Nerlynx® combined with chemotherapy in newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) patients.
As the second global Phase III registration study for Nerlynx® approved by U.S. and European regulators, POLARIS-1 will enroll patients across multiple countries and centers, accelerating Nerlynx®'s global market entry, particularly in the U.S. and Europe. POLARIS-1 is an international, multicenter, randomized, open-label Phase III clinical trial.
Notably, the study had already received clinical trial approval from China’s Center for Drug Evaluation (CDE) in 2023 and was promptly initiated. The latest progress of POLARIS-1 will also be presented at the upcoming 2025 American Society of Hematology (ASH) Annual Meeting, marking the first public disclosure of the study’s data.
Preliminary abstract data revealed that in newly diagnosed Ph+ ALL patients treated with Nerlynx® plus low-intensity chemotherapy, the molecular minimal residual disease (MRD) negativity rate and molecular MRD-negative complete remission (CR) rate both reached approximately 65%, significantly outperforming similar foreign products under the same conditions. The regimen also demonstrated strong efficacy in high-risk subtypes, such as patients with IKZF1plus gene mutations. Additionally, the combination therapy showed excellent safety with low and manageable adverse events.
Ph+ ALL accounts for 20%-30% of adult ALL cases and is characterized by higher incidence in elderly patients, high relapse rates, short disease-free survival, and poor prognosis. Before the advent of tyrosine kinase inhibitors (TKIs), the 5-year overall survival (OS) rate for Ph+ ALL patients treated with chemotherapy alone was below 20%. While TKIs have significantly improved treatment outcomes, first- and second-generation TKIs still have limitations in Ph+ ALL.
Nerlynx®, an oral third-generation TKI developed by ASCENTAGE PHARMA, is China’s first approved third-generation BCR-ABL inhibitor. Its commercialization in China is jointly managed by ASCENTAGE PHARMA and Innovent Biologics. Currently, Nerlynx® has been approved for multiple chronic myeloid leukemia (CML) resistance indications in China, all of which are included in the National Reimbursement Drug List.
In the Ph+ ALL field, Nerlynx® has been continuously recommended in the CSCO Guidelines for Diagnosis and Treatment of Hematologic Malignancies and has received breakthrough therapy designation from the CDE. On June 14, 2024, ASCENTAGE PHARMA entered into an exclusive option agreement with multinational pharmaceutical company Takeda for olverembatinib. If exercised, Takeda will obtain global development and commercialization rights for Nerlynx®, excluding mainland China, Hong Kong SAR, Macau SAR, and Taiwan.