China-based Junshi Biosciences (HKG: 1877, SHA: 688180) has announced that the National Medical Products Administration (NMPA) has accepted a clinical trial filing for JS401, an injectable co-developed with partner Risen Pharma. The product is an ANGPTL3 mRNA-targeted small interfering RNA (siRNA) designed to treat hyperlipidemia.
JS401: Mechanism and Development
JS401 targets angiopoietin-like 3 (ANGPTL3), a protein expressed by the liver that regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL). By specifically degrading ANGPTL3 mRNA in hepatocytes via N-acetylgalactosamine (GalNac) delivery, JS401 continuously inhibits the expression of ANGPTL3, thereby reducing triglyceride and cholesterol levels in the blood. This mechanism positions JS401 as a potential novel therapy for hyperlipidemia.
Market Landscape and Competitive Position
Currently, only Evkeeza (evinacumab-dgnb), an ANGPTL3-targeted monoclonal antibody developed by Regeneron, is commercially available for treating homozygous familial hypercholesterolemia (HoFH) in patients aged 12 years and above. No siRNA product targeting ANGPTL3 has been approved for marketing. However, Novartis’s Leqvio (inclisiran), a PCSK9-targeted siRNA drug approved in the European Union and the US in 2020 and 2021, respectively, has entered the Bo’ao Lecheng pilot zone in China for special use. JS401 aims to fill the gap in ANGPTL3-targeted siRNA therapies.-Fineline Info & Tech
