Ascentage Pharma's olverembatinib (HQP1351) has received approval for inclusion in China's 2024 National Reimbursement Drug List (NRDL) for a new indication: adult patients with chronic-phase chronic myeloid leukemia (CML-CP) who are resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs). Effective January 1, 2025, this decision expands the drug's availability to a broader patient population in China. The original indication for CML-CP or accelerated-phase CML (CML-AP) harboring the T315I mutation will maintain its reimbursable status.
Olverembatinib, a third-generation BCR-ABL inhibitor developed by Ascentage Pharma, is the first such therapy approved in China. It effectively targets BCR-ABL and a spectrum of BCR-ABL mutants, including the T315I mutation, which is a common cause of TKI resistance. The drug received its initial approval in China in November 2021 for T315I mutant CML and subsequently in November 2023 for CML-CP resistant and/or intolerant to earlier generation TKIs. Ascentage Pharma and Innovent Biologics are jointly commercializing olverembatinib in China.
Addressing TKI Resistance in CML
Chronic myeloid leukemia (CML) is a hematologic malignancy affecting white blood cells. While the introduction of BCR-ABL TKIs has significantly improved CML management, resistance to these therapies remains a significant challenge. Studies indicate that 20%-40% of patients fail to achieve desired treatment outcomes due to resistance or intolerance to TKIs, leading to disease progression or even death.
"We are glad that the new indication of olverembatinib has been included into the NRDL through the simple contract renewal process," said Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma. "This decision reaffirms the importance of olverembatinib as an innovative drug that has the potential to fulfill the urgent unmet needs and treatment gaps in CML."
Clinical Development and Future Prospects
Olverembatinib is currently approved in China for TKI-resistant CML-CP or CML-AP with the T315I mutation, and for CML-CP resistant and/or intolerant to first- and second-generation TKIs. The drug is also being investigated for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), with a global Phase III study underway for newly diagnosed patients. Additionally, a global Phase III study is evaluating olverembatinib for succinate dehydrogenase- (SDH-) deficient gastrointestinal stromal tumor (GIST), for which it has received Breakthrough Therapy designation in China.
Olverembatinib has garnered significant interest from the hematology community, with clinical results presented at the American Society of Hematology (ASH) Annual Meetings for seven consecutive years. The US FDA has granted the drug four Orphan Drug Designations and a Fast Track Designation, while the EMA of the EU has granted one Orphan Designation. In February 2024, the US FDA cleared olverembatinib for a global registrational Phase III study.
In June 2024, Ascentage Pharma and Takeda entered into an Exclusive Option Agreement for olverembatinib, potentially granting Takeda global rights to develop and commercialize the drug outside of mainland China, Hong Kong China, Macau China, and Taiwan China.
