News | Pharmaceuticals | January 04, 2022

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

Leqvio is a first-in-class small interfering RNA (siRNA) therapy for LDL-C reduction and sustained reduction of up to 52% vs. placebo

Novartis' inclisiran (Leqvio)

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:


Related LDL-lowering Drug News:

VIDEO: Novel Therapeutics for Lowering Lipids — Interview with Susan Cheng, M.D.

Inclisiran Reduced LDL-C in Obese Patients

New Novartis Data for Inclisiran Shows Effective and Sustained LDL-C Reduction at 17 Regardless of Age or Gender

Two-Dose a Year LDL-lowering Drug Had Significant Impact in Pooled Analysis of ORION Trials

What Trends are Ahead in Cardiovascular Medicine in 2018?

VIDEO: Use of Genetic Testing to Tailor Lipid Lowering Therapies

ORION 1 Trial Shows Inclisiran Lowers Bad Cholesterol Up to One Year

Two-Dose a Year LDL-lowering Drug Had Significant Impact in Pooled Analysis of ORION Trials

FDA Clears Bempedoic Acid Non-statin LDL-cholesterol Lowering Drug



1. Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507-1519. doi:10.1056/NEJMoa1912387.

2. Raal FJ, Kallend D, Ray KK, et al. Inclisiran for heterozygous familial hypercholesterolemia. N Engl J Med. 2020;382(16):1520-1530. doi:10.1056/NEJMoa1913805.

3. Wong ND, Young D, Zhao Y, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012. J Clin Lipidol. 2016;10(5):1109-1118. doi: 10.1016/j.jacl.2016.06.011.

4. Grundy MS, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/ AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–e1143. doi: 10.1161/CIR.0000000000000625.

5. Khvorova A. Oligonucleotide therapeutics — a new class of cholesterol-lowering drugs. N Engl J Med. 2017;376(1):4-7. doi: 10.1056/NEJMp1614154.

6. Kosmas CE, Muñoz Estrella A, Sourlas A, et al. Inclisiran: a new promising agent in the management of hypercholesterolemia. Diseases. 2018;6(3):63. doi: 10.3390/diseases6030063.

7. World Health Organization. Cardiovascular diseases (CVDs). June 11, 2021. Accessed November 23, 2021.

8. National Kidney Foundation. Global Facts: About Kidney Disease. Accessed November 23, 2021.

9. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives—a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72(3):247-259. doi: 10.1038/

10. World Health Organization. Diabetes. November 10, 2021. Accessed November 23, 2021.

11. Accessed November 23, 2021.

12. World Health Organization. Cardiovascular diseases: Data and statistics.  Accessed November 23, 2021.

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