Recently, Hengrui Pharmaceutical and its subsidiary Fujian Shengdi Pharmaceutical Co., Ltd. received the "Clinical Trial Approval Notice" issued by the National Medical Products Administration, approving clinical trials of Hengrui's independently developed Class 1 innovative drug HRS-4729 injection in patients with metabolic associated fatty liver disease/metabolic associated steatohepatitis. Currently, no similar products have been approved for market globally.
Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) is a chronic progressive liver disease caused by nutritional excess and insulin resistance in genetically susceptible individuals. Epidemiological studies show that the global pooled prevalence rate reached 30.05% from 1990 to 2019, while China's prevalence rate reached 32.9% in 2018. MASLD interacts with metabolic syndrome and type 2 diabetes, significantly increasing the risk of liver-related clinical events, cardiovascular-renal-metabolic related diseases, and non-hepatic malignancies, leading to increased all-cause mortality and has become a major public health challenge requiring urgent attention.
As important regulatory hormones for human energy metabolism, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon (GCG) can activate corresponding receptors in multiple organs including the central nervous system, pancreatic islets, intestines, liver, and adipose tissue, synergistically regulating insulin secretion, appetite suppression, energy expenditure, and other functions. Based on this mechanism, multi-agonists simultaneously targeting GLP-1, GIP, and GCG receptors achieve synergistic effects through multiple pathways, not only significantly enhancing weight loss and glucose-lowering efficacy, but also demonstrating broad therapeutic potential in improving hepatic lipid metabolism, suppressing inflammatory responses, and even reversing liver fibrosis.
HRS-4729 injection is a Class 1 innovative drug independently developed by Hengrui Pharmaceutical, functioning as a GLP-1R/GIPR/GCGR triple receptor agonist. Compared to GLP-1R/GIPR dual receptor agonists, the triple receptor agonist adds GCGR target activation on the basis of regulating glucose and lipid metabolism and suppressing appetite in vivo, which can further enhance systemic and hepatic metabolic improvement effects, potentially providing new treatment options for patients and clinicians.
In May last year, the company licensed the exclusive rights for global development, production, and commercialization of its proprietary GLP-1 class innovative drug portfolio, including HRS-4729, outside the Greater China region to Kailera Therapeutics in the United States. The upfront payment plus potential milestone payments could total up to $6 billion, and the company also acquired a 19.9% equity stake in Kailera. Additionally, HRS-4729 for overweight/obesity has received clinical trial approval and is currently advancing Phase I trials in China.
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