Lerodalcibep

Lerodalcibep is a novel, third-generation PCSK9 inhibitor engineered as a recombinant fusion protein. It consists of a specific PCSK9-binding domain, known as an adnectin, fused to human serum albumin (HSA). The adnectin component binds with high affinity to proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of cholesterol metabolism that normally promotes the lysosomal degradation of low-density lipoprotein receptors (LDLR) on the hepatocyte surface. By inhibiting the interaction between PCSK9 and the LDLR, lerodalcibep prevents receptor degradation, thereby increasing the abundance and recycling of LDLRs. This upregulation of hepatic LDLRs enhances the clearance of circulating LDL cholesterol (LDL-C). The fusion with human serum albumin serves a critical pharmacokinetic function by preventing rapid renal clearance and extending the drug's plasma half-life, which facilitates a convenient dosing regimen compared to native peptides.