ARC-AAT

ARC-AAT is an investigational RNA interference (RNAi)-based therapeutic developed for the treatment of liver disease associated with alpha-1 antitrypsin deficiency (AATD), a rare genetic disorder that can cause severe liver and lung damage in both children and adults. The drug employs a novel unlocked nucleobase analog (UNA) containing RNAi trigger molecule, delivered systemically using Arrowhead Pharmaceuticals' proprietary Dynamic Polyconjugate delivery platform. Its mechanism involves silencing the expression of the alpha-1 antitrypsin (AAT) gene in hepatocytes, thereby reducing hepatic production of the mutant Z-AAT protein, which is believed to be responsible for progressive liver disease in AATD patients. Preclinical and early clinical studies have shown that ARC-AAT can achieve deep, durable, and dose-dependent knockdown of AAT production—up to 90% reduction at higher doses—potentially halting or reversing progression of liver disease by preventing accumulation of toxic Z-AAT protein[1][2][4][5][6][8].