FDA Approves Inclisiran (Leqvio) Label Update as First-Line Monotherapy in Hypercholesterolemia

Novartis has announced the US Food and Drug Administration (FDA) approval of a label update for inclisiran (Leqvio), enabling its use as monotherapy along with diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia.1

According to a July 31, 2025, release from the Company, the FDA proactively requested the label update based on the robust LDL-C lowering data for PCSK9-targeting therapies. Specifically, the updated label removes the requirement for inclisiran to be used on top of or in combination with statin therapy and revises "primary hyperlipidemia" to the more specific term of "hypercholesterolemia" throughout the label to more accurately focus on LDL-C reduction.1

"This first-line label update reinforces [inclisiran]’s proven ability to effectively lower LDL-C, a critical risk factor for heart disease," Victor Bultó, President, US, Novartis, said in a statement.1 "With this new indication enabling [inclisiran]’s use as monotherapy along with diet and exercise, we now have the potential to help even more patients achieve their LDL-C lowering goals earlier in their treatment journey."

Inclisiran is an injectable prescription medicine indicated as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). Novartis has obtained global rights to develop, manufacture, and commercialize inclisiran under a license and collaboration agreement with Alnylam Pharmaceuticals.1

The initial approval for inclisiran occurred in December 2021, approval and indicated the agent for reducing LDL-C. The approval was 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.2

Inclisiran received a subsequent label expansion from the FDA in 2023 for primary hyperlipidemia, which allowed for expanded use as an adjunct to diet and statin therapy beyond the previously approved ASCVD and HeFH patient populations.3

The July 2025 label update removes the requirement to be used on top of or in combination with statin therapy, with additional updates including the revision of "primary hyperlipidemia" to "hypercholesterolemia" throughout the label to enhance focus on LDL-C reduction.

As described by Novartis, with its twice-yearly, health care provider-administered dosing, inclisiran is uniquely positioned to help support patient adherence and long-term LDL-C management, including goal attainment. This is a critical unmet need, as up to 80% of ASCVD patients in the US struggle to reach the LDL-C guideline-recommended target of <70 mg/dL. Of note, this need is highlighted by the latest 2025 ACC/AHA Joint Committee Clinical Practice Guideline for the Management of Patients with Acute Coronary Syndromes, which recommends more aggressive treatment to achieve LDL-C targets.1

Novartis is advancing multiple studies evaluating the potential use of inclisiran across primary and secondary prevention. In 2024, the company announced positive data from twice-yearly inclisiran in the phase 3 V-MONO study, which met its primary endpoints.

In the study, inclisiran monotherapy achieved clinically meaningful and statistically significant LDL-C lowering versus both placebo and ezetimibe in patients who were at low or moderate risk of developing atherosclerotic cardiovascular disease (ASCVD) and not receiving lipid-lowering therapy.4

Additionally, VICTORION-1-PREVENT is the only dedicated study of a non-statin lipid-lowering therapy in a high-risk primary prevention population as defined by American College of Cardiology (ACC) and American Heart Association (AHA) guidelines. In the secondary prevention setting, the ORION-4 and VICTORION-2-PREVENT outcomes studies are on track for data readouts in 2026 and 2027, respectively.4

References

1. PR Newswire. Novartis twice-yearly* Leqvio® (inclisiran) receives FDA approval for new indication enabling first-line use. July 31, 2025. Accessed July 31, 2025. https://www.prnewswire.com/news-releases/novartis-twice-yearly-leqvio-inclisiran-receives-fda-approval-for-new-indication-enabling-first-line-use-302519118.html

2. Center for Drug Evaluation and Research. FDA approves add-on therapy to lower cholesterol in certain people. U.S. Food and Drug Administration. December 22, 2021. Accessed July 31, 2024. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-add-therapy-lower-cholesterol-among-certain-high-risk-adults.

3. Novartis United States of America. US FDA approves expanded indication for Novartis Leqvio® (Inclisiran) to include treatment of adults with high LDL-C and who are at increased risk of heart disease. Novartis United States of America. July 10, 2023. Accessed July 31, 2025. https://www.novartis.com/us-en/news/media-releases/us-fda-approves-expanded-indication-novartis-leqvio-inclisiran-include-treatment-adults-high-ldl-c-and-who-are-increased-risk-heart-disease.

4. Novartis. Novartis twice-yearly* Leqvio® demonstrated clinically meaningful, statistically significant LDL-C lowering as a monotherapy in patients at low or moderate ASCVD risk. August 28, 2024. Accessed July 31, 2025. https://www.novartis.com/news/media-releases/novartis-twice-yearly-leqvio-demonstrated-clinically-meaningful-statistically-significant-ldl-c-lowering-monotherapy-patients-low-or-moderate-ascvd-risk