Transcript
Dr Knowlton:
Hello, everyone. My name is Dr Kirk Knowlton.
I’m a general cardiologist, professor of clinical investigation and medical director of cardiovascular research at Intermountain Health in Salt Lake City, Utah.
In this video, we will be focusing on timely intervention to reduce low-density lipoprotein cholesterol, or LDL-C, following a coronary event.
I will begin with the clinical overview of LEQVIO and then review findings from V-INCEPTION. As the principal investigator of this trial, I am eager to help disseminate these results widely and to discuss how this data can directly impact clinical decision-making and, ultimately, how we can help care for our patients following a coronary event.
I believe there are 2 critical components to LDL-C management after a coronary event in patients with atherosclerotic cardiovascular disease, or ASCVD. First, patients with ASCVD should receive guideline-recommended lipid-lowering therapy.
And second, early treatment post event to reach the LDL-C target is key. The 2025 ACC/AHA guidelines make this very clear, stressing the importance of moving beyond statins if necessary.
Before we take a closer look at the latest LEQVIO LDL-C reduction data in patients soon after their coronary event, let’s go over the Indication and Important Safety Information.
INDICATION
LEQVIO® (inclisiran) injection is indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce low-density lipoprotein cholesterol (LDL-C).
IMPORTANT SAFETY INFORMATION
LEQVIO is contraindicated in patients with a prior serious hypersensitivity reaction to inclisiran or any of the excipients in LEQVIO. Serious hypersensitivity reactions have included angioedema. Adverse reactions in clinical trials (≥3% of patients treated with LEQVIO and more frequently than placebo) were injection site reaction, arthralgia, and bronchitis.
Please see LEQVIO full Prescribing Information on this site or at www.leqviohcp.com.
Dr Knowlton:
Let’s first take a closer look at the data from the pivotal trials. The ORION-10 and ORION-11 pivotal trials evaluated the efficacy and safety of LEQVIO in patients with established ASCVD or increased risk of cardiovascular disease. Patients were on maximally tolerated statin, with or without ezetimibe, and still required additional reduction to get to the LDL-C target of less than 70 mg/dL. Other non-statin therapies were excluded in these trials. The primary efficacy measure was the percentage change in LDL-C from baseline to Day 510.
From the ORION-10 clinical trial, we saw that LEQVIO demonstrated powerful and consistent LDL-C reduction throughout each 6-month dosing interval, with a 52% difference in LDL-C reduction from baseline compared to placebo at Month 17.
Additionally, in ORION-10, 84% of patients with ASCVD who were treated with LEQVIO achieved LDL-C levels less than 70 mg/dL at Month 17 compared with 18% of placebo-treated patients. As for the results from ORION-11, they were consistent with ORION-10.
Also, in ORION-10, 75% of patients receiving LEQVIO achieved the LDL-C target of less than 55 mg/dL compared with 4% of patients on placebo at Month 17. Results were similar in patients with ASCVD in ORION-11. These results clearly demonstrate that LEQVIO can help achieve lower LDL-C levels.
V-INCEPTION took the pivotal trial findings a step further by focusing specifically on patients screened within 5 weeks after their coronary event, giving us critical insights into early intervention with LEQVIO. V-INCEPTION was a 12-month, randomized, open-label Phase 3b study that evaluated the efficacy and safety of LEQVIO plus usual care versus usual care alone in patients who needed additional LDL-C lowering after a coronary event. The co-primary end points of the study were percentage change in LDL-C from baseline to Day 330 and the proportion of patients achieving the prespecified LDL-C target of less than 70 mg/dL at Day 330.
V-INCEPTION reflects real-world practice because the study design allowed clinicians to manage patients as they normally would in practice. This means that, in both the LEQVIO plus usual care arm and the usual care alone arm, providers had the autonomy to titrate or adjust treatments based on their patients’ needs. Usual care included statin and non-statin lipid-lowering treatment as considered appropriate by treating clinicians. However, by the end of the study, unfortunately about 68% of patients in the usual care alone group remained on statins alone, with a minority of patients receiving additional non-statin lipid-lowering therapy.
The results from the V-INCEPTION trial demonstrated that addition of LEQVIO to the patients’ LDL-C management plan shortly after a coronary event reduced LDL-C consistent with pivotal trials. At Day 330, the LEQVIO arm demonstrated a 47% LDL-C reduction difference from usual care alone. Nearly 70% of patients in the LEQVIO arm met the LDL-C target of less than 70 mg/dL, compared to 28% of patients in the usual care alone arm.
Additionally, over half of the patients in the LEQVIO arm achieved an LDL-C target of less than 55 mg/dL compared with 14% of patients receiving usual care alone.
Safety is always the other side of the coin, and it’s equally important. In the Phase 3 pivotal studies, LEQVIO was observed to be well tolerated over 18 months. The most common adverse reactions were injection site reactions, arthralgia, and bronchitis. The encouraging news is that the safety profile of LEQVIO in V-INCEPTION was consistent with pivotal trials with no new safety signals. Understandably, like any clinical trial, this open-label study does have its limitations. Usual care did not reflect “best practice,” with little use of guideline-recommended, non-statin therapy—therefore, a comparison of efficacy or safety of LEQVIO vs other non-statin therapies cannot be made. Not all participants in the LEQVIO arm received 3 doses of LEQVIO, and LEQVIO use was not restricted in the usual care alone arm. The open-label design presented with inherent limitations, including higher dropout rates.
The results make one thing clear—in the usual care arm, where treating clinicians could adjust therapy as appropriate, “best practice” was not reflected. This is because there was little use of guideline-recommended addition of non-statin therapy in patients that needed them, leaving those patients above their LDL-C goal. This reinforces the overarching and urgent need to improve usual care for patients.
Overall, we can do better. In V-INCEPTION, initiating LEQVIO within 5 weeks of a coronary event helped patients lower LDL-C, with many reaching guideline-recommended LDL-C targets by the end of the study. Thank you for watching, and let's continue to strive for better patient care.
References:
- Data on file. Novartis Pharmaceuticals Corp; 2025.
- Data on file. ORION-10. Novartis Pharmaceuticals Corp; 2025.
- Knowlton KU, Navar AM, Anderson JL, et al. LDL-C management with inclisiran plus usual care vs usual care alone in participants with recent acute coronary syndrome. VICTORION-INCEPTION. Presented at: National Lipid Association's 2025 Annual Scientific Sessions; May 29-June 1, 2025; Miami, FL.
- Leqvio. Prescribing information. Novartis Pharmaceuticals Corp.
- Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Eng J Med. 2020;382(16):1507-1519.
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