On April 23, 2024, the National Medical Products Administration (NMPA) of China formally approved Vebreltinib Enteric-coated Capsules (brand name: Wanbirui, hereinafter referred to as Vebreltinib), a Class 1 innovative drug independently developed by Beijing Purun'ao Biotech Co., Ltd.—a wholly-owned subsidiary of Beijing Ansai Biotech Co., Ltd. The indication is for the treatment of adult patients with IDH-mutant astrocytoma (WHO Grade 4) harboring the PTPRZ1-MET fusion gene or glioblastoma with a history of lower-grade disease, who have failed prior therapies. This marks the second indication approved for Vebreltinib in China following its approval for non-small cell lung cancer (NSCLC), and also represents the first fully approved small-molecule targeted therapy for MET-targeted treatment of glioma in China.
Treatment Bottleneck in Glioma Therapy
Glioma is a refractory primary malignant intracranial tumor, accounting for approximately 46% of all intracranial tumors[1]. Surgery, radiotherapy and chemotherapy constitute the traditional therapeutic strategies for glioma, yet the prognosis remains dismal. The 5-year overall survival (OS) rate of patients with malignant glioma is less than 10%[2]. Previous studies have identified MET fusions in about 12% of glioma cases[3]. Among them, the representative subtype PTPRZ1-MET fusion (hereinafter referred to as ZM fusion) occurs in approximately 14% of glioblastoma cases with a history of lower-grade disease. It is frequently concurrent with MET exon 14 skipping mutations and is associated with an even poorer prognosis.
Vebreltinib is a highly selective c-Met inhibitor independently developed in China. It was previously granted conditional approval for the treatment of patients with locally advanced or metastatic NSCLC harboring mesenchymal-epithelial transition factor (MET) exon 14 skipping mutations. Based on positive results from the pivotal phase II/III registrational clinical trial for glioma, the New Drug Application (NDA) for Vebreltinib was accepted by the Center for Drug Evaluation (CDE) of NMPA and included in the priority review procedure on October 16, 2023. Subsequently, Vebreltinib completed the transition from priority review listing to marketing approval in just over six months. This achievement not only affirms the value of Vebreltinib as an innovative targeted therapeutic agent, but also reflects its focus on the unmet clinical needs of the rare disease population with glioblastoma. Furthermore, it embodies the implementation of China’s key reform measures for the marketing approval of innovative drugs.
First MET-TKI Approved for Glioma Indication in China
The approval of Vebreltinib for the treatment of ZM fusion-positive glioma is grounded in the positive results of the FUGEN study (NCT06105619). The FUGEN study is a randomized, controlled, open-label, multicenter phase II/III registrational clinical trial led by the team of Academician Jiang Tao from Beijing Tiantan Hospital, Capital Medical University.
As of December 2023, a total of 84 patients were enrolled in the trial. This randomized controlled study compared the safety and efficacy of Vebreltinib monotherapy versus dose-dense temozolomide regimen or etoposide plus cisplatin regimen. The results demonstrated that compared with the control regimens, Vebreltinib monotherapy achieved a median overall survival (mOS) of 6.31 months, versus 3.38 months in the control group, representing a 48% reduction in the risk of death and significantly improving survival outcomes in patients with ZM fusion-positive glioma. The treatment was generally well-tolerated, with most common adverse reactions being Grade 1–2 and manageable/reversible through clinical intervention.
Driven by Dual Indications
In 2014, the team of Academician Jiang Tao from Beijing Tiantan Hospital, Capital Medical University first discovered the ZM fusion gene and reported it globally. The team identified this fusion as one of the key driver genes for the progression of glioma from lower-grade to higher-grade malignancy, making a landmark contribution to the discovery and development of molecular pathology for glioma. Concurrently, Academician Jiang Tao’s team collaborated with Ansai Biotech to conduct in-depth research on this pathogenic driver gene, successfully developing the first-in-class drug Vebreltinib and launching clinical research programs to evaluate its application in the field of glioma.
