If Successful, Inclisiran Primary Prevention Trial Could Expand Patient Population by More than 22 Million

Data from the European Society of Cardiology (ESC) Congress 2024 suggests more than 22 million US adults could be eligible for and benefit from inclisiran (Leqvio) if its ongoing primary prevention trial were to prove successful.

Presented at the meeting by Rahul Aggarwal, MD, of Brigham and Women’s Hospital, results shed light on the potential role of inclisiran as well as differences between eligible patient populations and the general US population.¹

“What we saw was that a lot of patients, around 23 million patients, in the US would meet enrollment criteria for VICTORION-1 PREVENT and so what that indicates is that there are a lot of patients who have high cardiovascular risk, who have lipid levels that are not well controlled yet, who could potentially benefit from therapy,” Aggarwal said, in an interview with HCPLive.

Initially approved in 2021 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 require additional lowering of LDL-C,inclisiran would go on to receive a subsequent label expansion indicating the agent for use as an adjunct to diet and statin therapy in patients with elevated LDL-C who have an increased risk of heart disease based on the VictORION program.^2,3

Launched in 2023 and expected to be completed in 2029, the VICTORION-1 PREVENT trial was designed to evaluate inclisiran in a primary prevention setting. With this in mind, the trial enrolled patients at high cardiovascular risk without a prior major atherosclerotic cardiovascular disease event and followed them after 1:1 randomization to inclisiran or placebo for a primary endpoint of 4-point major adverse cardiovascular events (MACE).⁴

In the ESC Congress 2024 study, Aggarwal and investigators sought to assess the generalizability of the trial’s enrollment criteria to the US population using data from the National Health and Nutrition Examination Survey. Using survey data recorded from 2015 through March 2020, investigators obtained data from more than 25,531 individuals.¹

Specific eligibility criteria from the trial included being a nonpregnant adult aged 40 to 79 years with LDL-C of 70 to 189 mg/dL with a 10-year risk greater than 20% or 7.5% to 19.9% with 2 risk-enhancing factors at baseline. Investigators calculated 10-year risk using the American Heart Association race-free 10-year PREVENT risk equations and defined risk-enhancing factors as Risk enhancing factors included high sensitivity C-reactive protein equal or greater than 2 mg/L, inflammatory arthritis, eGFR less than 60 ml/min/1.73 m2, metabolic syndrome, or early family history of cardiovascular disease.¹

Using NHANES data, investigators estimated 21,576,506 (SE, 1,258,255) adults met eligibility criteria for VICTORION-1 PREVENT. According to investigators, this is representative of 8.8% of all US adults or 15.1% of all US adults aged 30 to 79 years. The cohort had a mean age of 65.3 (SE, 0.5) years and 55.0% (SE, 2.5%) were female.¹

Relative to the US adult population, the meeting eligibility criteria for the trial had greater mean BMI (32.6 [SD, 0.3] kg/m2 vs 29.5 [SD, 0.2] kg/m2), greater rates of obesity (61.0% [SD, 2.1%] vs 40.0% [SD, 1.1%]), greater mean systolic blood pressure (133.9 [SD, 1.0] mmHg vs 121.7 [SD, 0.3] mmHg), greater rates of hypertension (85.8% [SD, 2.0%] vs 45.9% [SD, 1.1%]), greater mean HbA1c (6.3 [SD, 0.1] vs 5.7 [SD, 0.02]), and greater rates of diabetes (39.7% [SD, 2.6%] vs 13.1% [SD, 0.7%]).¹

Aggarwal has no relevant disclosures to report.

References:

1. R Aggarwal, DL Bhatt, M Bonaca, et al. Applicability of VICTORION-1 PREVENT Criteria to the US Population. Presented at: European Society of Cardiology Congress 2024. August 30 - September 2, 2024. London, UK.
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 October 2, 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 October 2, 2024. 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. A study of Inclisiran to prevent cardiovascular events in high-risk primary prevention patients. Novartis. Accessed October 2, 2024. https://novartis.com/clinicaltrials/study/nct05739383.