AZD8233

AZD8233 is an antisense oligonucleotide (ASO) designed to inhibit the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of low-density lipoprotein cholesterol (LDL-C). By targeting PCSK9 mRNA in the nucleus, AZD8233 reduces circulating PCSK9 protein levels, which leads to increased LDL receptor availability and lower LDL-C concentrations in the blood. This mechanism aims to reduce cardiovascular risk in patients with hypercholesterolemia or dyslipidemia who are at high risk for major cardiovascular events and may not achieve target LDL-C levels with statins alone. The drug utilizes Ionis Pharmaceuticals' Generation 2.5 chemistry and LICA technology for enhanced potency and liver targeting[1][2][4][7]. It was developed as a next-generation PCSK9 inhibitor acting upstream of current monoclonal antibody therapies by suppressing gene expression rather than neutralizing circulating protein[2][5]. Clinical trials demonstrated significant reductions in both PCSK9 (~89%) and LDL-C (~73%) but development has been discontinued for all indications[4].

Other names

AZD8233 (for subcutaneous formulation)ION449ION-449ION 449