FDA Approves Twice-Yearly Inclisiran (Leqvio) for Lowering Cholesterol in ASCVD, HeFH

Announced on December 22, the approval of inclisiran (Leqvio) comes nearly a year after the original PDUFA date. With approval, inclisiran becomes the first and only siRNA therapy approved to lower LDL-C with twice-yearly dosing.

Inclisiran (Leqvio) has received approval from the US Food and Drug Administration (FDA) for lowering LDL-C in patients with atherosclerotic cardiovascular disease or heterozygous hypercholesterolemia, according to a statement from Novartis.

Nearly a year after the original PDUFA date, inclisiran becomes the first and only small interfering RNA therapy approved to lower LDL-C with twice-yearly dosing. The indication from the FDA is for use as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical ASCVD or HeFH who require additional lowering of LDL-C.

“ASCVD is a substantial public health burden affecting 30 million Americans,” said Norman Lepor, MD, a Los Angeles-based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio, in the aforementioned statement. “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.”

Among the most highly anticipated approvals in recent memory, inclisiran has remained in the spotlight since Novartis acquired The Medicines Company in 2019 for $9.7 billion. The road to approval has been longer than Novartis may have initially hoped for, with the company receiving a CRL ahead of their original December 2020 PDUFA date. A statement from Novartis noted the FDA did not cite concerns related to the efficacy or safety of inclisiran, but FDA expressed concerns related to unresolved facility inspection-related conditions. About 7 months later in July 2021, the company announced their Complete Response resubmission for inclisiran.

The December 22, 2021, approval for inclisiran is based on data from the ORION-9, -10, and -11 clinical trials, which enrolled more than 3400 participants with ASCVD or HeFH. In these trials, inclisiran was associated with a sustained reduction of LDL-C up to 52% compared to placebo therapy.

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

Novartis noted twice-yearly maintenance doses of inclisiran can be administered following an initial dose and an additional dose at 3 months. Novartis expects inclisiran to be available in early January 2022.

“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.”