Transcript
Dr Burkle:
Hello. I’m Dr Jaime Burkle. I am excited to be here for this discussion. In this video, we will highlight key data that demonstrate how LEQVIO®, or inclisiran, may be an option for managing elevated LDL-cholesterol levels and share our clinical experiences and perspective regarding the importance of cholesterol management for the right patient at the right time.
Dr Alraies:
I’m Dr Chadi Alraies. It’s a pleasure to be here with Dr Burkle.
Dr Burkle:
Before we begin, let’s review the Indication and Important Safety Information for LEQVIO.
Voiceover:
INDICATION: LEQVIO (inclisiran) injection is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH)
IMPORTANT SAFETY INFORMATION
Contraindication: 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 anaphylaxis and angioedema.
Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylaxis and angioedema, have been reported in patients treated with LEQVIO. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to seek medical attention promptly.
Adverse Reactions: Adverse reactions in clinical trials (≥3% of adult patients treated with LEQVIO and more frequently than placebo) were injection site reaction, arthralgia, and bronchitis.
Please see LEQVIO full Prescribing Information available on this site or at LEQVIOHCP.com.
Dr Alraies:
LEQVIO can be used as an LDL-cholesterol–lowering therapy, with or without a statin, as an adjunct to diet and exercise. In my practice, this is meaningful because it allows me to better tailor my LDL-C treatment strategy to meet patient needs. I appreciate that I can consider LEQVIO for LDL-cholesterol lowering from the start, whether I prescribe it concomitantly with a statin or with no statin at all.
Dr Burkle:
I agree! Many patients have persistently elevated LDL-cholesterol levels, may be on a maximally tolerated statin therapy, and have multiple comorbidities with a high treatment burden. But I emphasize that LDL-cholesterol is one of the most modifiable risk factors for ASCVD and that we have treatment options available. When I think of who might be an appropriate patient for an LDL-cholesterol–lowering therapy, I focus on patients with elevated LDL-C who have had a recent cardiovascular event (within the past 12 months), those with a prior event at any time, patients diagnosed with ASCVD who have had no prior events, and also patients who are at risk of developing ASCVD.
Dr Alraies:
I agree, Dr Burkle. In my opinion, although it varies case to case, we should test early and often. And immediately after a coronary event can be the ideal time to initiate a therapy such as LEQVIO for patient who remain above LDL-cholesterol target. LEQVIO is a PCSK9 inhibitor, a first-in-class, small interfering RNA therapy with a unique mechanism of action that targets the liver by using the body’s natural RNA interference process. LEQVIO has been proven to lower LDL-cholesterol and is well tolerated in clinical trials.
Dr Burkle:
Absolutely—and what’s just as exciting is how seamlessly it fits into our clinical practice. When we look at our available treatment options, LEQVIO is the only twice-yearly LDL-cholesterol–lowering therapy that provides 6 months of LDL-cholesterol reduction therapy in a single dose, after 2 initial doses. There is broad coverage and affordability for most patients. Your Medicare Part B patients are eligible to start LEQVIO, with or without a statin.
Dr Alraies:
I would like to share a case that reflects what I often see in my own practice. Let’s take a look at Chris’s LDL-cholesterol–lowering journey and talk through how his treatment unfolded. Chris is a 65-year-old male who is obese and hypertensive. Because of his comorbidities, he is already taking blood pressure medications and a GLP-1 agonist for his weight loss. His LDL-cholesterol level was 140 milligram per deciliter, so he was started on 20 milligrams atorvastatin daily. At the time of Chris event, 3 years ago, he presented to the emergency department with shortness of breath and chest pain and he was scheduled for an immediate PCI. Following procedure, Chris was diagnosed with ASCVD. Chris’s LDL-cholesterol level was tested at the time of the event. When the lab came back with a result of 110 milligram per deciliter, his statin dose was escalated to 40 milligram daily. For someone like Chris, with multiple risk factors and now a coronary event, I would really want to see his LDL-cholesterol below 55 milligram per deciliter to better align with the current targets.
At his follow-up visit, about three months after the event, Chris’s LDL-cholesterol was 95 milligram per deciliter—still above the guideline-recommended target. His statin dose was increased, but even with that adjustment, it was clear he was not at goal. Data show that there is only incremental reduction to LDL-cholesterol level when moving from moderate to high intensity statin. So although Chris’s statin dose was doubled, this will only yield marginal benefit. He need an additional LDL-cholesterol–lowering therapy to get him to goal. At this point, Chris started on LEQVIO. Chris’ profile is very similar to those patients studied in the ORION-10 clinical trial, and so from my clinical perspective, this was a straightforward decision.
Let’s first go through the pivotal trial data for LEQVIO, and then I can share Chris’ story, which was in line with the results seen in the clinical trials. LEQVIO was studied in two Phase 3, multicenter, double-blind and randomized, placebo-controlled, 18-month trials, ORION-10 and ORION-11.
ORION-10 enrolled patients who had ASCVD. ORION-11 also enrolled patients with ASCVD and included patients with increased risk of ASCVD. All patient were receiving maximal tolerated statin therapy with or without ezetimibe and required additional LDL-C lowering.
Patients were randomized to receive subcutaneous injection of either LEQVIO or placebo at Day 1, 3 months later (which is Day 90), and then every 6 months (Day 270 and Day 450). In the ORION-10 study, LEQVIO demonstrated powerful and consistent LDL-cholesterol reduction throughout each 6-month dosing interval, with a 52% LDL-cholesterol reduction difference from placebo at Month 17.
Also, 84% of patient treated with LEQVIO achieved guideline-recommended LDL-cholesterol target of lower than 70 milligram per deciliter at Month 17, compared with 18% of placebo-treated patients. These results were similar in the ORION-11 study.
As for Chris, he followed a very similar trend to what was seen in ORION-10 study results. With the addition of LEQVIO to his ongoing statin therapy, Chris experienced about an additional 50% reduction in his LDL-cholesterol, which align with the results seen in clinical trials at Month 17. His levels are now well below the guideline-recommended target of 70 milligram per deciliter. Now, Chris is seen every 6 months for his LEQVIO administration and routine LDL-cholesterol monitoring.
Dr Burkle:
Let’s discuss another case now, Denise—she’s a 67-year-old female with hypertension and hypercholesterolemia who had an initial LDL-cholesterol level of 140 milligrams per deciliter. She smokes. She is taking now a statin and an ACE inhibitor. Denise had a greater than 20% 10-year ASCVD risk score which puts her at increased risk of ASCVD. Denise may have been experiencing symptoms, like chest discomfort and shortness of breath, which triggered a referral for a coronary computed tomography angiography, which is CCTA, to check for blockages or narrowing of her coronary arteries. She also had a coronary calcium scan, which came back with a score of 340. The results from the CCTA indicated subclinical atherosclerosis, and she was indeed diagnosed with ASCVD.
Now, Denise is being seen for follow-up appointments every 6 months to monitor her cholesterol. A year ago, she shared that she was trying to improve her diet and exercise regimen, and she also had quit smoking. Her levels had decreased to 126 milligrams per deciliter at her follow-up appointment 6 months later. So despite statin therapy, her LDL-C level was not at the guideline-recommended level. So she was started on ezetimibe to try to further reduce her LDL-C. But at her follow-up appointment, her LDL-C level was still at 110 milligrams per deciliter. So at this point, it was important to take further action for Denise’s care and to get and stay at her LDL target. In my mind, this was a great opportunity to suggest LEQVIO based on the results seen in the LEQVIO pivotal trials that showed approximately 50% LDL-cholesterol reduction difference from placebo at Month 17. The goal was to get Denise to an LDL-C target of less than 70 milligrams per deciliter. So after the decision was made to start her on LEQVIO, coverage under traditional Medicare was verified, and the process was straightforward, allowing Denise to begin treatment without delay.
The addition of LEQVIO to Denise’s management plan reduced her LDL levels by approximately 50%. Denise has now been on LEQVIO for over 2 years and continues to see her LDL-C level remain below target.
Based on Phase 3 clinical trials over 18 months, LEQVIO was shown to be well tolerated. The most common adverse reactions occurring in greater than or equal to 3% of patients treated with LEQVIO and more frequently than placebo were injection site reaction, arthralgia, and bronchitis. The majority of adverse events in each trial were reported to be mild to moderate. LEQVIO had a low discontinuation rate due to adverse reactions, which occurred in 2.5% of patients treated with LEQVIO versus 1.9% of patients receiving placebo. Injection-site reactions were the most common cause for treatment discontinuation and were observed in 0.2% of patients treated with LEQVIO versus 0% of patients taking placebo.
Dr Alraies:
LEQVIO can integrate seamlessly into patients’ existing clinical care visits, which are usually every 6 months, so they don’t have to schedule additional appointment. One dose of LEQVIO is administered initially, again at 3 months, and then every 6 months. Once administered, there is no chance of a missed dose for 6 months. My patient prefer the 2 injections a year after the 2 initial doses instead of more frequent injections. Only LEQVIO is the HCP-administered, and I know that for a patient like Chris or Denise, who may not want to self-inject and/or have high polypharmacy burden, have the clinician administer the injection provides both the clinician and patient with the confidence that their doses were received. And in-office administration may help with consistent follow-up and interaction when patients return for their subsequent doses, potentially improving long-term continuity of care.
Dr Burkle:
Many patients, similar to Denise, struggle with adherence to statin therapy because they may not be confident that is a treatment or if it’s working for them. For Denise, an appropriate treatment option, such as LEQVIO, is one that not only has proven efficacy to help her to get to her LDL-cholesterol on target and stay there, but also one that she can get administered by her health care professional; and this way they both can be confident that she does receive her dose. Denise has had a high medication burden for years, and putting Denise on LEQVIO provides her with the opportunity to get her injection on same day as her cardiology visit.
Dr Alraies:
And Chris is a frequent traveler, so the dosing schedule for LEQVIO works well for him. He values continuity, so he schedules regular office visits, occurring every 6 months, for both his LEQVIO injection and, when needed, his lab work.
Dr Burkle:
I hope this conversation offered a meaningful insight and compelling data on LEQVIO as an LDL-cholesterol–lowering treatment option for your patients with ASCVD—whether or not they’ve experienced a prior cardiovascular event.
The LEQVIO Digital Education Library provides additional resources to explore LEQVIO data and the insights of health care professionals. Visit CVPerspectives.com to learn more about the topics discussed today.
References:
- Centers for Medicare & Medicaid Services. Medicare Benefit Policy Manual. Baltimore, MD: US Dept of Health and Human Services; 2003. Accessed March 31, 2026.
- Data on file. LEQVIO coverage and affordability. Novartis Pharmaceuticals Corp; 2025.
- Data on file. ORION-10 Clinical Study Report. Novartis Pharmaceuticals Corp; 2019.
- Data on file. ORION-11 Clinical Study Report. Novartis Pharmaceuticals Corp; 2019.
- Fox KM, Tai M-H, Kostev K, et al. Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins. Clin Res Cardiol. 2018;107(5):380-388.
- Khvorova A. Oligonucleotide therapeutics - a new class of cholesterol-lowering drugs. N Engl J Med. 2017;376(1):4-7.
- Leqvio. Prescribing information. Novartis Pharmaceuticals Corp.
- Nexletol. Prescribing information. Esperion Therapeutics, Inc.
- Nexlizet. Prescribing information. Esperion Therapeutics, Inc.
- Praluent. Prescribing information. Regeneron Pharmaceuticals, Inc.
- Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. [Erratum published in: Circulation. 2025;151(13):e865. Erratum published in: Circulation. 2025;151(25):e1098. Erratum published in: Circulation. 2025;152(19):e402.]
- Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(16):1507-1519.
- Ray KK, Wright RS, Kallend D, et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;382(suppl):1-31.
- Repatha. Prescribing information. Amgen Inc.
- Romanelli RJ, Ito MK, Karalis DG, et al. Statin utilization and low-density lipoprotein cholesterol in statin-treated patients with atherosclerotic cardiovascular disease: trends from a community-based health care delivery system, 2002-2016. J Clin Lipidol. 2020;14(3):305-314.
- Underberg J, Toth PP, Rodriguez F. LDL-C target attainment in secondary prevention of ASCVD in the United States: barriers, consequences of nonachievement, and strategies to reach goals. Postgrad Med. 2022;134(8):752-762.
- Wright RS, Raal FJ, Koenig W, et al. Inclisiran and administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial. Cardiovasc Res. 2024;120(12):1400-1410.
- Wright RS, Ray KK, Raal FJ, et al. Pooled patient-level analysis of inclisiran trials in patients with familial hypercholesterolemia or atherosclerosis. J Am Coll Cardiol. 2021;77(9):1182-1193.
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