Cardiometabolic & Renal
Cardiometabolic disease is the leading cause of death in the United States. A common cause of cardiometabolic disease is atherosclerosis, or premature plaque buildup, which occurs when cholesterol and inflammatory cells accumulate in blood vessels. Researchers have shown a strong correlation between high cholesterol levels and subsequent cardiometabolic diseases. As such, lowering cholesterol is a key component in preventing and managing cardiometabolic disease.
Cardiometabolic disease is an area of focus for us. We have created a cardiometabolic disease franchise comprised of drugs that target all the key components of cardiometabolic disease, including various atherogenic lipids, inflammation and thrombosis, an aberrant blood clot formation responsible for most heart attacks and strokes. We have designed the majority of the drugs in our cardiometabolic franchise to target cardiometabolic risk factors. These drugs make up our lipid franchise and include IONIS-APO(a)Rx and IONIS-ANGPTL3Rx. Recent additions to our lipid franchise are our drugs that lower Lp(a) and angiopoietin-like 3 protein, or ANGPTL3. Lp(a) is another independent risk factor for cardiometabolic disease. ANGPTL3 is a genetically validated target shown to play a significant role in regulating lipid levels. Humans who do not produce a functional ANGPTL3 protein due to a genetic mutation have extremely low levels of cholesterol, LDL-C, and very low levels of triglycerides and HDL-cholesterol. Currently available lipid-lowering therapies do not significantly lower apoC-III, triglycerides, Lp(a), or ANGPTL3. We believe that reducing levels of apoC-III, Lp(a) and ANGPTL3 could provide a complimentary approach to lipid-lowering therapies, including KYNAMRO(R). We are also developing follow-on LICA antisense drugs for the three drugs in our lipid franchise.
In order to maximize the value of our lipid franchise, while also maintaining control over the development and commercialization of these assets, we have created a wholly owned subsidiary, Akcea Therapeutics. Akcea is focused on the development and commercialization of our lipid franchise drugs and their follow on compounds.
In addition to our lipid franchise drugs, we have a promising anticoagulant agent, IONIS-FXIRx, in development in our cardiometabolic disease franchise. We recently reported Phase 2 data on IONIS-FXIRx showing that IONIS-FXIRx-treated patients experienced a seven-fold lower incidence of venous thromboembolism and numerically fewer bleeding events compared to patients treated with enoxaparin, a commonly used anticoagulant. These data demonstrate that for the first time, an anticoagulant, IONIS-FXIRx, can prevent clotting without increasing bleeding, two biological events that were previously inseparable. Our latest drug to enter the franchise, IONIS-AGT-LRx, offers a novel approach to treating patients with high blood pressure.