Chemistry: Generation 2+ LICA
IONIS-APOCIII-LRx, formerly known as AKCEA-APOCIII-LRx, is a ligand-conjugated (LICA) investigational antisense medicine designed to inhibit the production of apoC-III for patients who are at risk for cardiometabolic disease due to elevated triglyceride levels. ApoC-III is a protein produced in the liver that regulates triglyceride metabolism in the blood and is an independent cardiovascular risk factor. People with elevated triglycerides are at increased risk for cardiovascular disease and for type 2 diabetes. People with severely elevated triglycerides, such as people with familial chylomicronemia syndrome (FCS), are at high risk for acute pancreatitis and other serious conditions. ApoC-III is also the target of WAYLIVRA, the first approved medicine for patients with FCS.
About ApoC-III and Triglycerides
ApoC-III is an important emerging target linking hypertriglyceridemia with cardiovascular disease (CVD). In several studies, apoC-III levels are an independent risk factor for CVD. Further, its presence on lipoproteins may increase their atherogenicity. A study in the New England Journal of Medicine reported that out of a sample of over 100,000 people, individuals with an apoC-III loss-of-function mutation had a reduced risk of clinical coronary heart disease. Each decrease of 1mg/dL in plasma levels of apoC-III was associated with a 4% decrease in the risk of incident coronary heart disease. Triglycerides may also play a role in cardiovascular risk. In two separate studies encompassing nearly 20,000 patients, as triglyceride levels increased, so did the risk of a cardiovascular event. In summary, apoC-III impacts triglyceride levels and may also increase inflammatory processes. This combination of effects makes apoC-III a valuable target for reducing the residual CVD risk in patients already on statin therapy, or for whom triglycerides are poorly controlled.