This marks the second BTD granted to olverembatinib by the CDE, with the first one 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). A New Drug Application (NDA) for this indication was accepted by the NMPA in July 2022 and subsequently granted a BTD that will support a full approval of olverembatinib. To date, olverembatinib has been granted two Priority Review Designations that underscored the drug's promising therapeutic utility.

BTDs are commonly granted to innovative drugs and 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 exchange, and in receiving guidance to advance the drug development progress. Furthermore, BTD-designated drugs will be eligible for Priority Review status and conditional approvals upon submission 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.

GIST is a type of malignancy that arises in mesenchymal tissues of the gastrointestinal tract, and most patients with GIST harbor KIT or PDGFRAmutations. The introduction of TKIs has significantly improved the prognosis of these patients. However, patients with SHD-deficient GIST, a rare subtype of GIST, still have considerable unmet medical needs. It is known to the research community that patients with SDH-deficient GIST are commonly insensitive to existing TKIs. Although patients with early-stage localized disease can benefit from surgical treatment, most of them eventually experience relapse^[1]-[5]. At present, there is no standard of care for patients with relapsed or advanced SDH-deficient GIST, whose 5-year event-free survival (EFS) is only 24%^[1]-[5].

Olverembatinib, a third-generation TKI being jointly commercialized in China by Ascentage Pharma and Innovent Biologics, is the first and only third-generation BCR-ABL inhibitor approved in China for the treatment of adult patients with TKI-resistant chronic-phase chronic myeloid leukemia (CML-CP) or accelerated-phase CML (CML-AP) harboring the T315I mutation. While being clinically developed and adopted for the treatment of hematologic malignancies, olverembatinib also showed potent antitumor activity against GIST in preclinical models and early clinical studies, including particularly promising efficacy in patients with SDH-deficient GIST. Results from an ongoing Phase Ib/II study of olverembatinib in China showed an impressive clinical benefit rate (CBR) of 93.8% in patients with this subtype of GIST^[6]. Based on these promising results, the study was selected for presentations at the American Society of Clinical Oncology (ASCO) Annual Meeting for two consecutive years. (Olverembatinib is an investigational drug that has not been approved for any indication in the US.)

"We are highly appreciative of the regulator's recognition of olverembatinib's clinical potential," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "This BTD indicates olverembatinib's promising therapeutic utility in SDH-deficient GIST, marking a major milestone in its clinical development for nonhematologic indications. Moving forward, we will maintain close contact with the CDE to expedite the clinical development program in China and allow patients to benefit from this novel therapeutic as soon as possible."