Four Drug Candidates Receive IND Approval and One NDA Submitted in China: Merck, Hengrui, CSPC, Gloria, and Xiangxue Announce Clinical and Regulatory Milestones

According to announcements from various companies and information from the CDE official website, four drugs have been approved for clinical trials, and one drug has been submitted for marketing! They are Merck's GLP-1R/GCGR dual agonist MK-6024 injection, CSPC's anti-tumor nano-innovative drug Cisplatin Micelle Injection, Yuheng Pharmaceutical/WuXi Biologics’ LAG3 monoclonal antibody, Guangzhou Xiangxue Pharmaceutical’s TCR-T product TAEST1901 injection, and Hengrui Medicine’s Irinotecan Liposome Injection.

Four Drugs Approved for Clinical Trials

Merck: GLP-1R/GCGR Dual Agonist Approved for Clinical Trials in China

According to the public information displayed on the CDE official website, the Class 1 new drug MK-6024 Injection submitted by MSD has been approved for clinical trials in China. The proposed indication for development is non-alcoholic steatohepatitis (NASH). Public data shows that MK-6024 (efinopegdutide) is a once-weekly GLP-1R/GCGR dual agonist, currently in Phase 2 clinical trials globally.

GLP-1R and GCGR are members of the G protein-coupled receptor family and serve as two key "regulators" for maintaining blood glucose balance in the human body. GLP-1R is the receptor for glucagon-like peptide-1 (GLP-1), which primarily functions after eating by binding to its ligand GLP-1, stimulating insulin secretion, lowering postprandial blood glucose, and maintaining it at normal levels. GCGR is the receptor for glucagon, which, during states of hunger, increases blood glucose levels by binding to its ligand glucagon.

Studies show that GLP-1R/GCGR dual agonists have multiple modes of action. They can not only increase insulin secretion and reduce food intake by activating GLP-1R, but also lower inflammation and fat production by activating GCGR. Currently, the dual agonist therapy targeting GLP-1R/GCGR has become a new direction for treating diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

Public data shows that with the prevalence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (commonly referred to as "fatty liver") has become one of the most common chronic liver diseases. Among these, NASH, an advanced form of NAFLD, is becoming a leading cause of cirrhosis and liver transplantation.

CSPC: Anti-tumor Nano Innovative Drug Approved for Clinical Trials

According to the announcement by CSPC Pharmaceutical Group, the Cisplatin Micelle Injection developed by its subsidiary, CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., has been approved by the National Medical Products Administration of the People's Republic of China to conduct clinical trials in China.

Cisplatin is a first-line drug for the treatment of various solid tumors, but its clinical application is limited by severe adverse reactions such as nephrotoxicity and neurotoxicity.The clinical indication approved this time is for advanced malignant solid tumors. This product falls under Category 2 of China's chemical drug registration classification, and currently, there are no similar products available on the global market.

Yuheng Pharmaceutical/WuXi Biologics: LAG3 Monoclonal Antibody Approved for Clinical Trials

According to the CDE official website, Yuheng Pharmaceutical's recombinant fully human anti-LAG-3 monoclonal antibody injection has been approved for clinical use to treat advanced malignant tumors.

LAG3 is an immune checkpoint, and similar to PD-1, it is an inhibitory target. The LAG3 monoclonal antibody can stimulate the body's immune system by binding to LAG3, playing a role in tumor suppression. Preclinical research data shows that inhibiting LAG3 can restore cytotoxicity in T cells, thereby enhancing their ability to kill tumors. LAG3 is currently one of the second-generation targets with substantial clinical data and relatively established drug feasibility, making antibody drugs targeting this site highly likely to become a significant anti-tumor treatment.

In November 2017, Yuheng Pharmaceutical and WuXi Biologics reached a collaboration to jointly develop a fully human innovative anti-LAG3 antibody drug. This is another collaboration between Yuheng and WuXi Biologics for the development of a new immune checkpoint antibody drug following their PD-1 antibody.

Xiangxue Pharmaceutical: TCR-T Product Approved for Clinical Trials

According to the announcement by Xiangxue Pharmaceutical, TAEST1901 Injection, an innovative product of its subsidiary GuangDong XIANGXUE LIFE SCIENCES LTD, has received clinical trial approval from China's National Medical Products Administration (NMPA). It is intended for the treatment of advanced liver cancer or other advanced tumors with HLA-A*02:01 tissue genotype and positive AFP tumor antigen expression. This marks the second TCR-T product from GuangDong XIANGXUE LIFE SCIENCES LTD to obtain clinical trial approval, following the TCR-T product TAEST16001 Injection.

TCR is the abbreviation for T cell receptor. The mechanism of TCR-T therapy is similar to that of CAR-T therapy, both involving the modification of a patient's own T lymphocytes in vitro, which are then reinfused into the patient’s body to kill tumors. Unlike most CAR-T therapies that target specific antigen proteins on the surface of cancer cells, TCR-T therapy can "target" a variety of antigen proteins both inside and outside the tumor. It can be used to treat solid tumors and even simultaneously address multiple tumor diseases across different areas.

According to the announcement, TAEST1901 injection is an affinity-enhanced TCR-T therapeutic product specific to HLA-A*02:01/AFP. The target is a complex composed of HLA-A*02:01 and AFP antigen peptides. It uses lentivirus-transduced autologous T cells to express AFP antigen-specific TCR. Alpha-fetoprotein (AFP) is a protein that is highly expressed in hepatocellular carcinoma cells, making it an ideal target for T-cell immunotherapy.

One Drug Application for Marketing Approval

Hengrui Medicine: Liposomal Irinotecan Hydrochloride Injection Submitted for Marketing Approval

According to Hengrui's official WeChat, the interim analysis results of Hengrui Pharmaceutical's randomized, double-blind, parallel-controlled, multi-center Phase III clinical study (HR-IRI-APC) of Irinotecan Hydrochloride Liposome Injection combined with 5-FU/LV as a second-line treatment for locally advanced or metastatic pancreatic cancer after failure of gemcitabine treatment have met the pre-specified superiority criteria. The study results show that Irinotecan Hydrochloride Liposome Injection combined with 5-FU/LV significantly extends patients' overall survival (OS) compared to placebo combined with 5-FU/LV.

Based on the significant efficacy and safety results from the Phase III study, Hengrui Medicine has submitted a drug marketing authorization application to the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA).

Irinotecan Hydrochloride Liposome Injection is a new formulation developed by Hengrui Medicine based on the existing marketed Irinotecan Hydrochloride Injection and its freeze-dried powder injection, which can be targeted to distribute in tumor tissues.

The HR-IRI-APC study enrolled 298 subjects, who were randomly assigned in a 1:1 ratio to the experimental group and the control group (149 subjects each). The experimental group received treatment with irinotecan hydrochloride liposome combined with 5-FU/LV administered once every two weeks, while the control group received placebo combined with 5-FU/LV administered once every two weeks. The primary endpoint of this study was overall survival (OS). Secondary endpoints included progression-free survival (PFS), time to treatment failure (TTF), objective response rate (ORR), changes in CA19-9 tumor marker response, quality of life score (QoL), and safety.

The study results showed that liposomal irinotecan hydrochloride injection combined with 5-FU/LV achieved a significant and clinically meaningful extension in OS compared to placebo combined with 5-FU/LV.

Editor: Qijin

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