ION839 (formerly IONIS-AZ6-2.5-LRx), also known as AZD2693, is an investigational ligand-conjugated antisense (LICA) medicine designed to inhibit the production of patatin-like phospholipase domain-containing 3 (PNPLA3) protein. PNPLA3 is a protein that is found on the surface of intracellular lipid droplets. Studies have shown that a common genetic mutation of PNPLA3 is strongly associated with an increased risk for non-alcoholic steatohepatitis (NASH), an accumulation of fat in the liver that causes liver damage. The mutant PNPLA3 protein is resistant to degradation, causing it to accumulate on the surface of lipid droplets, which disrupts the normal process for degrading lipid droplets, leading to increased liver fat accumulation, the underlying pathology of NASH. In a mouse model of NASH that results from the expression of mutant PNPLA3, intervention with an antisense drug targeting PNPLA3 reduced hepatic mutant protein expression. This inhibition of mutant protein expression reduced liver fat accumulation, inflammation, and fibrosis, all hallmarks of NASH pathology in the mutant mouse model.
About Non-Alcoholic Steatohepatitis (NASH)
NASH is a common liver disease characterized by liver steatosis, inflammation and scarring. NASH is associated with an increased risk of cardiovascular disease and can lead to more severe diseases such as cirrhosis and liver failure.
Safety and efficacy have not been evaluated by any regulatory authorities for the indications described.
