Novartis announced the US Food and Drug Administration (FDA) approval of Leqvio (inclisiran), the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months. Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway. Leqvio reduces the amount of LDL-C in the bloodstream by improving the liver’s natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high. It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months. This approach may help those who have trouble sticking to medicines that are self-administered and have greater dosing frequency. Leqvio will be available in early January 2022. The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy. In the Phase III trials at month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% vs. placebo and was reported to be well-tolerated with a safety profile shown to be comparable to placebo. The most common side effects were mild to moderate injection site reaction (including pain, redness and rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms and shortness of breath. Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.