Visirna's siRNA Drug VSA003 Granted Breakthrough Therapy Designation by CDE for HoFH

January 2, 2024Day 9Weierzhen Biotechnology (Shanghai) Co., Ltd. ("Weierzhen" or "Visirna") announced that its innovative small nucleic acid drug under development, VSA003 Injection (hereinafter referred to as VSA003), has been included in the list of breakthrough treatment drugs by the Center for Drug Evaluation (CDE) of the National Medical Products Administration. The drug is intended for the treatment of homozygous familial hypercholesterolemia (HoFH).

HoFH is a severe autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in key genes responsible for the catabolism of low-density lipoprotein cholesterol (LDL-C). Patients are exposed to extremely high levels of LDL-C from an early age, significantly increasing the risk of atherosclerotic cardiovascular disease (ASCVD). This can lead to angina or myocardial infarction during childhood, adolescence, or adulthood, with significant mortality and disability, posing a serious threat to the patient's life and health. The extreme elevation of LDL-C in the vast majority of HoFH patients is due to the loss or defect of function in the low-density lipoprotein receptor (LDLR). The mechanisms of action of existing lipid-lowering drugs are mostly LDLR-dependent; therefore, their lipid-lowering efficacy in HoFH patients often falls short of expectations, showing obvious clinical limitations.

VSA003 is a small interfering RNA (siRNA) drug targeting angiopoietin-like protein 3 (ANGPTL3). Through a dual lipid-lowering mechanism that is both LDLR-independent and LDLR-dependent, its lipid-lowering effect is not influenced by LDLR function and can effectively reduce LDL-C levels in HoFH patients. VSA003 has been included in the list of breakthrough therapy drugs, and its clinical development and review process will be further accelerated, with the potential to become the world's first approved siRNA drug targeting the ANGPTL3 pathway.

"Visirna is very grateful to the CDE for recognizing the potential clinical value of VSA003 and including it in the list of breakthrough therapies," said Dr. Zou Xiaoming, CEO of Visirna. "This is the second innovative small nucleic acid drug developed by Visirna to be included in the list of breakthrough therapies after VSA001. Visirna is currently actively preparing for the pivotal Phase III clinical trial of VSA003 in HoFH and other dyslipidemia indications, and will accelerate the clinical development of VSA003 in China through active communication with regulatory agencies and close cooperation with research institutions and clinical experts, to provide better treatment options for Chinese HoFH and broader dyslipidemia patients as soon as possible."

Regarding Breakthrough Therapy Drugs

Breakthrough therapy drugs refer to innovative or improved new drugs used for the prevention and treatment of diseases that seriously endanger life or significantly affect the quality of life, and for which there are no effective means of prevention or treatment, or which have sufficient evidence of significant clinical advantages compared with existing treatments. The CDE provides the following support measures for products included in the breakthrough therapy drug review process during the R&D and marketing phases: 1. The Drug Evaluation Center will prioritize related communication and exchanges, enhance guidance, and promote the drug R&D process; 2. In the marketing application phase, these drugs can apply for a priority review process, reducing the review time limit to 130 days; 3. During the marketing application stage, data can be submitted on a rolling basis, with priority inspections and tests, etc.

About Homozygous Familial Hypercholesterolemia (HoFH)

HoFH is a rare autosomal dominant genetic disorder. Compared with general cardiovascular disease patients, HoFH patients are exposed to extremely high LDL-C levels from birth, significantly increasing the risk of atherosclerotic cardiovascular disease (ASCVD); moreover, their systemic ASCVD onset occurs at a young age and progresses rapidly, potentially leading to angina or myocardial infarction during childhood or adolescence, with death often occurring before the age of 20 to 30. It poses significant mortality and disability risks among children, adolescents, and adults alike, seriously endangering the health and lives of patients. The prevalence of HoFH is approximately 1/300,000 to 1/160,000 and has been included in the "First List of Rare Diseases" jointly formulated by five departments, including the National Health Commission of China.

The main treatment methods for HoFH currently include a healthy lifestyle, medications, lipoprotein apheresis, liver transplantation, and other surgical treatments. The "Chinese Guidelines for Lipid Management (2023)" indicate that statins form the foundation of cholesterol-lowering drug therapy; when statins fail to achieve the target LDL-C levels, non-statin lipid-lowering drugs can be used in combination, such as cholesterol absorption inhibitors (e.g., ezetimibe) or proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors); additionally, antioxidant drugs (e.g., probucol), bile acid sequestrants, niacin, and fibrates can also serve as alternative medications. Studies have shown that approximately 85-90% of HoFH patients experience extreme elevation of LDL-C due to loss-of-function or defective LDLR1. The mechanisms of action of existing lipid-lowering therapies are mostly LDLR-dependent, thus their lipid-lowering efficacy is limited in HoFH patients, and there are certain limitations regarding safety and medication adherence.

About VSA003

VSA003 is an siRNA drug that specifically targets ANGPTL3 mRNA in hepatocytes, effectively reducing the production of ANGPTL3 protein and decreasing the levels of ANGPTL3 protein in the liver and circulation. This reduction leads to: ① Inhibition of TRL (including VLDL, a precursor to LDL) secretion from the liver into the bloodstream, thereby lowering blood LDL-C and TG levels; ② Enhancement of LPL activity, increasing the hydrolysis of TG/TRL in peripheral tissues (such as adipose and muscle), thus reducing blood TG/TRL levels; ③ Enhanced uptake and clearance of LDL by hepatocytes primarily through LDLR-independent/EL-dependent pathways, as well as LDLR-dependent/EL-independent mechanisms for LDL-C, thereby reducing a series of key lipid indicators including LDL-C, VLDL-C, and TG. The target of VSA003, ANGPTL3, differs from the targets of statins, PCSK9 inhibitors, cholesterol absorption inhibitors, antioxidants, bile acid sequestrants, niacin, and fibrates recommended in the "Chinese Guidelines for Lipid Management (2023)," and it can reduce LDL-C via an LDLR-independent pathway.

About Visirna

Visirna is a small nucleic acid drug therapy company based in China with a global outlook, aiming to build a biopharmaceutical enterprise with comprehensive capabilities in research and development, production, and commercialization. The company was founded in 2022 and has established a long-term strategic partnership with Arrowhead Pharmaceuticals (NASDAQ: ARWR), an internationally leading small nucleic acid drug company. Currently, the company’s product pipeline includes three small nucleic acid drugs targeting cardiovascular and metabolic diseases, all at the clinical development stage. The company’s existing pipeline holds a leading position among similar competing products, with its research targets supported by clear genomic and biological evidence. It also utilizes Arrowhead Pharmaceuticals' proven chemical modification and delivery technology platforms. By adopting a U.S.-China coordinated clinical development and registration strategy, the company accelerates the registration and market launch of its products under development. Additionally, through the comprehensive integration of internal and external resources, it establishes an end-to-end industrial chain layout covering early R&D, clinical R&D, localized production, and commercialization.