FDA Approves LDL Cholesterol Lowering Inclisiran Injections

The treatment reduces the amount of LDL-C in the bloodstream by improving the liver’s ability to prevent protein production, which plays a role in keeping circulating cholesterol levels high.

The US Food and Drug Administration (FDA) has approved inclisiran (Leqvio) as the first ever small interfering RNA (siRNA) that lowers cholesterol with 2 subcutaneous injections doses per year.

The approval was awarded to Novartis and indicated as an adjunct to diet and maximally tolerated statin therapy for adult patients with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional low-density lipoprotein cholesterol lowering.

“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,” Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program, said in a statement.

The treatment reduces the amount of LDL-C in the bloodstream by improving the liver’s ability to prevent protein production, which plays a role in keeping circulating cholesterol levels high.

In a 2019 interview with HCPLive®, R. Scott Wright, MD, professor of Medicine & Cardiology at the Mayo Clinic and author on the ORION-10 study, explained how the novel treatment works.

“So, inclisiran is a drug which harnesses the body's natural ability to silence message RNA translation,” he said. “So it's a small RNA inhibitor, and it works by going into the apadosite, where it turns off the transcription of message RNA for PCSK9 through a complex called RSC.”

For dosing, patients will receive an injection at baseline, then 3 months later, followed by 1 dose every 6 months.

The approval was based on the ORION-9, -10 and -11 clinical trials, which included 3457 patients with ASCVD or HeFH with elevated LDL-C who are receiving a maximally tolerated dose of statin therapy.

The investigators found at month 17 inclisiran resulted in LDL-C reduction of up to 52% compared to placebo. The treatment was also well-tolerated with a safety profile similar to placebo. Common side effects included mild to moderate injection site reactions, joint pain, urinary tract infections, diarrhea, chest cold, pain in legs or arms, and shortness of breath.

The approval comes more than a year after the FDA issued a Complete Response Letter (CRL)for the application due to unresolved facility inspection-related conditions.