Olverembatinib (HQP1351): BCR-ABL/KIT Kinase Inhibitor for Chronic Myeloid Leukemia (CML), Acute Lymphoblastic Leukemia (ALL) and Gastrointestinal Stromal Tumors (GIST)

Acquired resistance to treatment is a significant and widely recognized challenge in the treatment of CML. Olverembatinib was engineered to address this challenge, demonstrating clinical efficacy in the presence of the key T315I mutation that confers resistance to most of the current tyrosine kinase inhibitor therapeutics. In addition to T315I mutation, olverembatinib has also shown clinical activity in disease characterized by multiple additional mutations and compound mutations. Beyond its efficacy in the treatment of resistant disease, olverembatinib has shown high potency in the management of treatment-naive CML expressing BCR-ABL, implicating for its potential for the first line therapy. Another advantage of olverembatinib demonstrated in clinic is its favorable safety profile in comparison with the counterparts. Therefore, since 2018, the clinical results of olverembatinib in drug-resistant CML 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. In July 2019, olverembatinib was cleared by the US food and Drug Administration (FDA) to directly enter a Phase Ib study for the treatment of drug-resistant CML.

In China, olverembatinib has been received approval in November 2021 for the treatment of adult patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. Subsequently, it was included into the China 2022 National Reimbursement Drug List (NRDL) for the approved indication. As the first and only approved third-generation BCR-ABL inhibitor in China, olverembatinib effectively ending the lack of treatment options for patients with T315I-mutated CML in the country. To date, this drug has been granted 2 Priority Review Designations and 2 Breakthrough Therapy Designations(BTD) by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA).

Beyond CML, olverembatinib also shows strong therapeutic potential in patients with Philadelphia chromosome-positive (Ph+) ALL and GIST. Recently, the global pivotal Phase III study of olverembatinib for the first-line treatment of Ph+ ALL has already been approved by the CDE. In GIST, the Clinical study of olverembatinib in succinate dehydrogenase (SDH)-deficient GIST was selected for presentation at the ASCO Annual Meeting for 2 consecutive years. Besides, this drug was granted a BTD by the CDE in June 2023 for the treatment of patients with SDH-deficient GIST who had received first-line treatment.

To date, olverembatinib has been granted one Fast Track Designation (FTD) and four Orphan Drug Designations (ODDs) from the US FDA for the treatment of CML, ALL, AML, and GIST; and one Orphan Designation from the European Medicines Agency (EMA) of the European Union for the treatment of CML.