Acceptance of Avistone's application for launch of MET inhibitor Vebreltinib enteric capsule (PLB-1001) in China

Author:Avistone  SeptemberRelease time:2022-09-28

Avistone recently announced the application by its subsidiary Purun'ao Biotechnology for the launch of its Vebreltinib enteric capsule. The application has been accepted on September 24 by the National Medical Products Administration for priority review. The proposed application of Vebreltinib is for the treatment of partial late-stage or metastatic NSCLC patient with Mesenchymal-epithelial transition factor (MET) Exon 14 skipping.

Non-small cell lung cancer (NSCLC) and irregular MET pathway

Lung cancer is the world's second most common type of cancer, and lung tumor is the most deadly tumor of all. Non-small cell lung cancer (NSCLC) makes up about 85% of lung cancer[1], with 3.0 % NSCLC patients also showing Mesenchymal-epithelial transition factor Exon 14 (METex14) skipping[2-3]. In China, about 1% of NSCLC patients are similarly inflicted[4]. With advances made with respect to clinical diagnosis, METex14 has become a hot target for the treatment of NSCLC.

MET stands for Mesenchymal-epithelial transition factor, also known as Hepatocyte Growth Factor Receptor (HGFR). It is a transmembrane receptor with autonomic phosphorylation activity produced by MET genetic coding, as well as a member of the super family of tyrosine kinase receptors. When combined with a ligand - hepatocyte growth factor (HGF), MET is activated through phosphorylation of dimer and certain points in the membrane-proximal region. It in turn activates a series of signal pathways in the downstream such as PI3K-Akt, Ras-MAPK and STAT, thereby causing cell multiplication, cell growth and angiogenesis.

Irregular activation of MET pathways typically includes MET 14 Exon skipping and mutation, MET amplification and MET protein over-expression.

Studies have shown that irregular activation of MET can cause multiplication, invasion and metastasis of tumor cells, ultimately leading to the occurrence and growth of malignant tumor. According to reports, impaired regulation of MET signal pathway has been observed in many types of solid tumors, such as those in lung cancer, gastric cancer, liver cancer, breast cancer, skin cancer and colorectal cancer. It also plays an important role in liver metastasis of colorectal cancer, formation, growth and metastasis of oral squamous cell carcinoma, invasion and metastasis of breast cancer, ovarian cancer and gastric cancer, as well as occurrence and growth of liver cancer, lung cancer and pancreatic cancer.

About Vebreltinib

Vebreltinib is a type of small-molecule selective MET inhibitor. It shows powerful effect with respect to inhibition of tumors in numerous pre-clinical MET irregularity in cell derived xenograft (CDX) model and patient-derived xenograft (PDX) model involving human gastric cancer, liver cancer, pancreatic cancer and lung cancer. The drug has been registered domestically in 7 clinical trials for indications including NSCLC and glioma.

In February 2021, Vebreltinib was included by CDE in breakthrough therapy to treat NSCLC involving MET Exon 14 skipping.

On September 14, 2022, Vebreltinib was included for priority review by CDE. On September 24, an application to register "Vebreltinib Enteric Capsule" as Category I new drug was accepted by CDE.

Key registration clinical trials for Vebreltinib have reached main conclusion, with it showing outstanding therapeutic effect and safety:

As of December 31, 2021, 52 cases of METex14 late-stage NSCLC patients who accepted Vebreltinib treatment (200mg BID) were included in full analysis set. At the preset main end points for the clinical trials, ORR as determined by IRC was as high as 75%, while DoR reached 16.7 months, and PFS was 12 months. Treatment data were superior to those of similar-class products.

Safety analysis data were based on consolidated, analyzed data in numerous local and overseas clinical trials for Vebreltinib. As of December 31, 2021, 310 late-stage NSCLC patients accepted treatment by Vereltinib at least once. The study results show that Vebreltinib possessed excellent overall safety, with the majority of adverse effects being grade 1-2, which can be managed clinically.

Dr. Hepeng Shi, CEO, and Founder of Avistone, said:

Dr. Shi Hepeng, Founder, Chairman and CEO of Avistone

The application for the launch of Vebreltinib for use in partial late-stage or metastatic NSCLC adult patients involving MET ex14 mutation signifies a major breakthrough in the field of MET irregularity. We should never forget our original vision, and should continue to explore lung cancer and other solid tumors with a view to serve more patients. We should continue to innovate in the service of humanity's health.


[1] Sung, H., et al., Global Cancer Statistics2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in185 Countries. CA: A Cancer Journal for Clinicians, 2021. 71(3): p. 209-249.
[2] Mark M. Awad, Geoffrey R. Oxnard, David M. Jackman, Daniel O. Savukoski, MET Exon 14 Mutations in Non–Small-Cell Lung Cancer Are Associated With Advanced Age and Stage-Dependent MET Genomic Amplification and c-Met Overexpression. Journal of clinical oncology 2016, 34: 721.
[3] Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer—a systematic review and meta-analysis. Lung Cancer 2018; 123: 76–82.

[4] Si-Yang Liu, Lan-Ying Gou, An-Na Li, Yi-Long Wu, The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC. Journal of Thoracic Oncology, 2016, 11:1503-1510.

Avistone Pharmaceuticals has two wholly-owned subsidiaries: Beijing Purun'ao Biotechnology Co., Ltd., established in 2012; Beijing Avistone Pharmaceuticals Biotechnology Co.,Ltd., established in 2018. Avistone is committed to the development of China's healthcare service industry and dedicated to providing high-quality medical products for patients. The company focuses on the research of anti-tumor drugs, and possesses several drug research pipelines. It mainly explores "First In Class" and "Best In Class" innovative drugs for lung cancer and glioma, among others. Avistone steadfastly devotes its effort to provide high-quality innovative drugs to make better life quality more accessible to patients. It aims to serve humanity health through continuous innovation. The company aims to contribute to the development of national pharmaceutical industry with its complete innovative drug research platform and through promotion of commercialization of its products.