FDA Approves Cholesterol-Lowering siRNA Therapy

FDA finally approved inclisiran (Leqvio), making it the first small interfering RNA (siRNA) therapy to hit the market for reducing LDL cholesterol, Novartis announced on Wednesday.

The PCSK9 inhibitor was handed an indication as an adjunct to diet and maximally-tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who need further lowering of LDL cholesterol.

The inclisiran regimen consists of an initial subcutaneous injection, another at 3 months, then a maintenance dose every 6 months thereafter — a more convenient schedule for heart patients compared with other PCSK9 inhibitors on the market.

“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,” said inclisiran investigator Norman Lepor, MD, of UCLA and Cedars-Sinai Medical Center, in a statement.

Notably, inclisiran’s approval had been delayed by a year because of FDA’s concerns with factory inspection issues.

The siRNA drug will be available in early January 2022 with Novartis manufacturing and commercializing it under a licensing agreement with Alnylam Pharmaceuticals.

Inclisiran’s approval was based on the phase III ORION-9, -10 and -11 clinical trials that included more than 3,000 patients. At month 17, inclisiran was associated with a halving of LDL cholesterol over placebo with no excess safety events.

The most common side effects were mild-to-moderate injection site reaction, joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms, and shortness of breath.

It remains to be seen whether inclisiran reduces cardiovascular morbidity and mortality. This is currently being studied in clinical trials, Novartis said.

European regulators had approved inclisiran at the end of 2020.