Heavy! The new indication of the innovative ADC SHR-A1811 is intended to be included in the breakthrough treatment variety

Recently, Hengrui Pharmaceutical's innovative ADC drug, SHR-A1811, for the treatment of advanced non-small cell lung cancer with HER2 mutation that has failed previous platinum-containing chemotherapy, was proposed to be included in the public list of breakthrough treatment varieties by the Drug Evaluation Center of the National Medical Products Administration.

The study was led by Professor Shun Lu from the Chest Hospital Affiliated to Shanghai Jiao Tong University and involved 10 centers across the country. Meanwhile, two other indications of SHR-A1811 have been included in the list of breakthrough therapies by the Drug Review Center of the National Medical Products Administration in February this year, namely, recurrent or metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) and recurrent or metastatic breast cancer with HER2 positive expression.

Lung cancer is currently the leading cause of cancer-related death in the world, and its morbidity and mortality have been increasing year by year. According to the data of GLOBOCAN2020, the incidence of lung cancer ranks the second among malignant tumors, and the mortality ranks the first among malignant tumors. The number of new cases of lung cancer in the world every year is about 2.207 million, and the number of death cases is about 1.796 million, ranking the first among the causes of death from tumors.

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer subjects, and the incidence of HER2 mutation lung cancer accounts for about 2% of non-small cell lung cancer (among which the incidence in China is 2.4-5.94%). This subtype is more common in lung adenocarcinoma and female non-smoking patients. Most of the mutations are exon 20 insertion mutations, which rarely coexist with other driver gene mutations such as EGFR, KRAS, BRAF, ALK, etc.

For patients with advanced NSCLC with HER2 mutation who failed previous platinum-containing chemotherapy, the benefit of monotherapy with Tyrosine kinase inhibitors (TKI, Tyrosine-Kinaseinhibitor), HER2 monoclonal antibodies and immune checkpoint inhibitors (not used in the first line) is limited, and the actual efficacy and safety of these drugs need to be confirmed by more data. In recent years, HER2 antibody conjugated drugs (HER2-ADC) have made great progress in the treatment of NSCLC with abnormal HER2 pathway, and this class of drugs is the research and development hotspot in this field.

SHR-A1811 for injection is a HER2-targeted antibody drug conjugate independently developed by Hengrui Pharmaceutical, which is intended to be used in the treatment of advanced solid tumors with HER2 expression or mutation. SHR-A1811 can specifically bind HER2 on the surface of tumor cells, and then the conjugate is endocytosed into the cells and transported to the lysosome, which induces the drug effect in tumor cells and induces the apoptosis of tumor cells through the drug carrier. SHR-A1811 has been approved for a number of phase I, II, and III clinical studies to provide a potential treatment option for cancer patients with HER2 gene abnormalities, and to provide additional clinical evidence for subsequent studies and benefits to patients.

Over the years, Hengrui has paid close attention to the treatment status of HER2-expressing or mutated tumors in China and continued to explore more effective treatment programs. In addition to SHR-A1811, the company currently has a number of innovative drug products in various solid tumor treatment areas, in order to bring more treatment options for patients.

What is breakthrough therapy designation?

In order to encourage the research and development of drugs with obvious clinical advantages, the Center for Drug Evaluation (CDE) of the State Medical Products Administration has issued the Announcement on the Release of three Documents, including the Procedures for the Evaluation of Breakthrough Therapy Drugs (Trial) (No. 82, 2020), which defines the scope of inclusion of breakthrough therapy: During drug clinical trials, innovative drugs or improved new drugs are used for the prevention and treatment of diseases that are seriously life-threatening or seriously affect the quality of life and for which there is no effective means of prevention and treatment or for which there is sufficient evidence of significant clinical advantages compared with existing treatment means. The Drug Review Center will communicate and communicate the priority allocation resources of drugs included in the breakthrough therapy drug program, strengthen guidance and promote drug development.