FDA Approves Label Update for Inclisiran as Monotherapy for Hypercholesterolemia

The FDA approved a label update for inclisiran (Leqvio), which can now be used as a monotherapy along with diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia. The FDA requested the label update due to data on the therapy’s ability to lower LDL-C.¹

The updated label also removes the requirement that inclisiran should be used on top of or in combination with statin therapies. | Image Credit: Anusorn - stock.adobe.com

"This first-line label update reinforces Leqvio's proven ability to effectively lower LDL-C, a critical risk factor for heart disease," Victor Bultó, president of US at Novartis, said in a news release.¹ "With this new indication enabling Leqvio'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."

The updated label removes the requirement that inclisiran should be used on top of or in combination with statin therapies. Other updates included revising primary hyperlipidemia to hypercholesterolemia to accurately focus on LDL-C reduction.¹

In the phase 3 V-MONO (NCT05763875) study, investigators aimed to determine if inclisiran could effectively reduce LDL-C from baseline to day 150 compared with the placebo or ezetimibe. The drug was studied as a 300 mg monotherapy dosage. Patients were screened for up to 14 days, entered a double-blind treatment period of 150 days, and had a safety follow-up conducted up to 30 days after the double-blind period. The primary end points included percentage change in LDL-C from baseline to day 150 compared with the placebo and ezetimibe. For secondary outcomes, investigators included absolute change from baseline to day 150, percentage change in proprotein convertase subtilisin/Kexin type 9 to 150 days, percentage change of non-high-density lipoprotein cholesterol (HDL-C) to 150 days, percentage change for total cholesterol/HDL-C ratio, percentage change in apolipoprotein B (Apo B) to day 150, percentage change in Apo B/Apo A-1 ratio to day 150, and percentage change in lipoprotein (a) to 150 days.²

Investigators found that monotherapy with inclisiran met its primary end point, showing reductions in LDL-C for patients who were not receiving lipid-lowering therapies. Patients included 350 patients who received randomized treatment 2:1:1, with 175 receiving inclisiran, 89 receiving ezetimibe, and 87 receiving the placebo.³ The mean percentage change in LDL-C from baseline was 1.4% for the placebo, –11.2% for ezetimibe, and –46.5% for inclisiran, according to the study authors. Inclisiran also demonstrated favorable improvements in other lipid and lipoprotein(a) levels. Further, the treatment had a favorable safety profile with no new safety concerns. The incidence of treatment-emergent adverse events was similar for inclisiran (31%), ezetimibe (30.3%), and placebo (28.7%).⁴

Furthermore, inclisiran showed that the drug also could be added to statin therapy and helped reduce LDL-C more than typical statin therapy alone in another study (NCT04929249). LDL-C reductions with inclisiran were at 60% compared with 7% for the usual care.³

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REFERENCES

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

2. Efficacy and Safety of Inclisiran as Monotherapy in Patients With Primary Hypercholesterolemia Not Receiving Lipid-lowering Therapy. (V-Mono). ClinicalTrials.gov identification: NCT05763875. Updated October 1, 2024. Accessed August 1, 2025. https://clinicaltrials.gov/study/NCT05763875

3. Biscaldi L. Inclisiran Monotherapy Significantly Reduces LDL-C in ASCVD. Drug Topics. August 28, 2024. Accessed August 1, 2025. https://www.drugtopics.com/view/inclisiran-monotherapy-significantly-reduces-ldl-c-in-ascvd

4. Taub PR, Gutierrez A, Wewers D, et al. Safety and Lipid-Lowering Efficacy of Inclisiran Monotherapy in Patients Without ASCVD: The VICTORION-Mono Randomized Clinical Trial. J Am Coll Cardiol. 2025;86(3):196-208. doi:10.1016/j.jacc.2025.04.049