Olverembatinib Granted BTD for Treatment of Ph+ ALL

This marks the third BTD granted to olverembatinib in China, with the first BTD granted in March 2021, for the treatment of patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant to first- and second-generation tyrosine kinase inhibitors (TKIs); and the second BTD granted in June 2023, for the treatment of patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) who had received first-line treatment.

BTDs are commonly granted to innovative drugs or modified novel drugs that are intended for the prevention or treatment of serious life-threatening diseases and/or conditions that severely impact the quality of life for which there is no existing treatment or where sufficient evidence indicates advantages over currently available treatment options. Drugs that have been granted BTDs are prioritized by the CDE in communications, and in receiving guidance to advance the drug development progress. Furthermore, if the applicant meets the relevant conditions after evaluation, BTD-designated drugs will be eligible for Priority Review status and conditional approvals upon submission of China’s version of a New Drug Application (NDA). In conclusion, granting of BTDs effectively accelerates development and review of innovative drugs and modified novel drugs presenting significant clinical value or addressing urgent unmet clinical needs.

The incidence rate of ALL in China is approximately 0.69/100,000; and Ph+ ALL, accounting for 20%-30% of all ALL cases in adults, is more common in the elderly with poor tolerance to treatment ¹ . Prior to the introduction of TKIs, a class of targeted small molecule compounds, the five-year overall survival (OS) rate of patients with Ph+ ALL treated with chemotherapy alone was below 20% ² . The clinical adoption of TKIs has resulted in a new clinical paradigm for patients with Ph+ ALL. The first- and second-generation TKIs still present considerable limitations, including a high relapse rate, short disease-free survival and poor prognosis. Moreover, no TKI has yet been approved for the first-line treatment of Ph+ ALL in China, resulting in a huge unmet medical need in the field.

Ascentage Pharma’s approved drug, olverembatinib, is the first China-approved third-generation BCR-ABL inhibitor and it is being jointly commercialized in China by Ascentage Pharma and Innovent Biologics. To date, olverembatinib has been approved in China for the treatment of adult patients with TKI-resistant CML-CP or accelerated-phase CML (CML-AP) harboring the T315I mutation and adult patients with CML-CP resistant to and/or intolerant of first- and second-generation TKIs. All approved indications have been included into the China National Reimbursement Drug List (NRDL).

In July 2023, the CDE cleared a global registrational Phase III study of olverembatinib in combination with chemotherapy versus imatinib in combination with chemotherapy for the treatment of patients with naïve Ph+ ALL, paving the way for olverembatinib to potentially become the first TKI approved in China for the treatment of Ph+ ALL in the first-line setting.

Reference

1. Theresa Liu-Dumlao, Hagop Kantarjian, et al. Philadelphia-positive acute lymphoblastic leukemia: current treatment options. Curr Oncol Rep. 2012 Oct;14(5):387-94.

2. Abou Dalle I et. Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia. Curr Treat Options Oncol2019 Jan 24;20(1):4.

Ascentage Pharma is a global, integrated biopharmaceutical company engaged in discovering, developing and commercializing therapies to address global unmet medical needs primarily in hematological malignancies. Ascentage Pharma has been listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK since October 2019 and has also been listed on the Nasdaq Global Market under the ticker symbol “AAPG” since January 2025.

The Company has built a rich pipeline of innovative drug candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53; and next-generation TKIs that target kinase mutants emergent during cancer treatment. Ascentage Pharma is also the only company in the world with active clinical programs targeting all known key apoptosis regulators. The Company has conducted more than 40 clinical trials in the US, Australia, Europe, and China, including 11 completed or ongoing US/global registrational trials on the company’s 5 key clinical-stage assets, of which 2 trials are regulated by the US FDA.

Olverembatinib, one of the company’s lead assets, is already approved in China with all of its approved indications included into the China National Reimbursement Drug List (NRDL). Olverembatinib is an investigational drug that has not been approved for any indication outside China.