The approval marks the first small interfering RNA therapy for low-density lipoprotein cholesterol reduction.
Inclisiran (Leqvio; Novartis) has become the first small interfering RNA (siRNA) therapy to be approved by the FDA to reduce low-density lipoprotein cholesterol (LDL-C) with 2 doses per year, following an initial dose and a dose at 3 months.
According to a press release, inclisiran is indicated 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 who require additional lowering of LDL-C. Researchers are also exploring the impact of inclisiran on cardiovascular morbidity and mortality.
“Leqvio is a revolutionary approach to lower LDL-C and creates new possibilities for how health care systems can impact cardiovascular disease, a defining public health challenge of our time,” said Vas Narasimhan, MD, CEO of Novartis, in the press release. “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.”
According to the press release, inclisiran reduces the amount of LDL-C in the bloodstream by improving the liver’s natural ability to prevent the production of proteins that keep circulating cholesterol levels elevated. It is administered as a subcutaneous injection given by a medical provider with an initial dose, followed by a dose at 3 months, and then doses every 6 months. This approach could help improve cholesterol levels in patients who struggle with adherence to self-administered medications.
“ASCVD is a substantial public health burden affecting 30 million Americans,” said Norman Lepor, MD, a cardiologist and clinical investigator in the phase 3 clinical program, in a press release. “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.”
The FDA approval is based on data from the comprehensive phase 3 ORION-9, -10, and -11 trials, in which all 3457 patients with ASCVD or heterozygous familial hypercholesterolemia had elevated LDL-C while receiving a maximally tolerated dose of statin therapy. According to the press release, at month 17, inclisiran delivered effective and sustained LDL-C reduction of up to 52% compared with the placebo.
Inclisiran was also reported to be well-tolerated with a safety profile comparable to that of the placebo. The most common adverse effects were mild to moderate injection site reaction including pain, redness, and rash; joint pain; urinary tract infection; diarrhea; chest cold; pain in the legs or arms; and shortness of breath.
“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, MS, BCPA, executive director of The Mended Hearts, Inc, in the press release. “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.”
FDA approves Novartis Leqvio (inclisiran), first-in-class siRNA to lower cholesterol and keep it low with two doses a year. News release. Novartis; December 22, 2021. Accessed January 4, 2022. https://www.novartis.com/news/media-releases/fda-approves-novartis-leqvio-inclisiran-first-class-sirna-lower-cholesterol-and-keep-it-low-two-doses-year