FDA Clears Novartis Inclisiran to Lower Cholesterol With Only Two Doses a Year

January 4, 2022 — The U.S. Food and Drug Administration (FDA) has cleared Novartis' inclisiran (Leqvio), the first small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (LDL-C) with two doses a year, after an initial dose and one at three months. The drug provides effective and sustained LDL-C reduction of up to 52% vs. placebo for certain people with atherosclerotic cardiovascular disease (ASCVD) on maximally tolerated statin therapy.[1,2]

Inclisiran is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with 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.

“ASCVD is a substantial public health burden affecting 30 million Americans,” said Norman Lepor, M.D., a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. “As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target.”

Approximately 16 million Americans with ASCVD taking statins to lower cholesterol—including those who have experienced a heart attack or stroke—are not at recommended LDL-C target.[3,4]

Inclisiran 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.[5,6] It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months1. 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.

“People with ASCVD have most likely experienced a heart attack or stroke from high cholesterol, causing a burden on the family and having a negative impact on lives,” said Andrea Baer, executive director of The Mended Hearts Inc. “One of the first steps to improving patients’ health is to manage high cholesterol and we’re encouraged that this new twice-a-year treatment offers a new option.” 

The FDA approval was based on results from the comprehensive Phase III ORION-9, ORION-10 and ORION-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.[1,2] In the Phase III trials at month 17, inclisiran 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.[3,4]

“Leqvio is a revolutionary approach to lower LDL-C, and creates new possibilities for how healthcare systems can impact cardiovascular disease, a defining public health challenge of our time,” said Vas Narasimhan, Novartis CEO. “We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C–lowering siRNA-based therapy to tackle ASCVD at scale across the United States.”

Novartis has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement with Alnylam Pharmaceuticals, a developer of RNAi therapeutics.

Leqvio is an Injectable Prescription for LDL-C

Inclisiran is an injectable prescription medicine indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical ASCVD or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of low-density lipoprotein cholesterol.

The effect of inclisiran on cardiovascular morbidity and mortality has not been determined.

The most common side effects of inclisiran were: injection site reaction (including pain, redness, and rash), arthralgia (joint pain), urinary tract infection, diarrhea, bronchitis, pain in legs or arms and dyspnea (shortness of breath).

Inclisiran (Leqvio) full prescribing information.

Cardiovascular Disease is World's Number One Killer

Cardiovascular (CV), renal and metabolic diseases are a global health crisis.[7-10] These chronic, complex and often hereditary diseases are frequently inter-related, and come with healthcare and treatment barriers and a lack of transformative medicines, and almost always lead to the same outcome: death due to CV disease.[7-10]

CV disease is the number one killer in the world.[7] Taking more lives than all cancers combined, it contributes to one in every three deaths globally.[7,11] Of all CV events, 80% can be prevented.[12]

For more information: www.novartis.us