Dr Saucier:
Hello and thank you for joining us for a discussion on “Real-World Evidence for LEQVIO (inclisiran): Clinical Insights on Why Adherence Matters”. I'm Dr Stephanie Saucier, a noninvasive cardiologist, a lipid specialist, and the director of the Women's Heart Wellness program at Hartford Healthcare Heart and Vascular Institute in Connecticut. I’m joined by my colleague Viet Le.
Viet:
Hello, I’m Viet Le. I'm a physician associate in preventive cardiology and an associate professor of research at Intermountain Health in Utah, where I codirect our preventive cardiology clinic. I'm also a sub-investigator in multiple Phase 3 clinical trials, including the ORION and VictORION studies for LEQVIO. Before we dive into today’s discussion about LEQVIO, let’s go over the Indication and Important Safety Information for LEQVIO.
INDICATION
LEQVIO or inclisiran injection is indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia or HeFH, to reduce low-density lipoprotein cholesterol or 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, which occurred in greater than or equal to 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 Saucier:
We know that elevated low-density lipoprotein cholesterol or LDL-C is one of the most modifiable risk factors for atherosclerotic cardiovascular disease, or ASCVD. An estimated 24 million people in the United States have ASCVD. So, it’s really important that we prioritize and work to lower patients’ LDL-C levels as soon as possible after a recent coronary event. LDL-C is a risk factor that can be silent over time, meaning patients might not have symptoms from their high cholesterol until that acute event. So, after the event, right away, it’s imperative to really change how they look at managing their LDL-C.
Viet, knowing how important LDL-C management is post cardiovascular event, how do you have impactful conversations with patients on the importance of lipid-lowering therapies?
Viet:
Yeah, I take them back to the angiogram, or revascularization, or the event itself to review their anatomy with them. I typically will show them where the blockages are and educate on the impact of elevated LDL-C and the urgency for LDL-C lowering. After an ASCVD event, that’s how I discuss the “what just happened” and “why LDL-C management is so important” to patients.
I think shared decision-making is really important because we’re educating the patients on their disease and the importance of medication. A patient really needs to understand why lowering their LDL-C is so important.
And this is a great example of how I approach shared decision-making. Educating our patients on their disease and the importance of medication may help empower them to take ownership of their health. When they understand the importance of lowering their LDL-C, in my experience, they are more likely to remain adherent to a medication.
Stephanie, once patients start on therapy, how do you overcome the challenges, such as nonadherence, we often face while working with our patients?
Dr Saucier:
As we know, despite statin therapy, patients with ASCVD continue to have elevated LDL-C levels, with 50% of patients discontinuing statin therapy within a year. Up to 80% of patients with ASCVD do not reach guideline-recommended LDL-C targets of less than 70 mg/dL. We need to be doing more to help our patients reach their LDL-C targets, especially since we know that 49% more total cardiovascular events were observed in patients who did not reach LDL-C targets. This is based on claims data from the Family Heart Database of over 38 million people that evaluated the annual cardiovascular event rates in a subset of guideline-defined high-risk patients from 2012 to 2021. I will note that the effect of LEQVIO on cardiovascular morbidity and mortality has not been determined.
With respect to my treatment approach, I always start my patients who have had a recent CV event on high-intensity statin therapy and repeat lipid panel anywhere from 4 to 8 weeks after initiation.
I’m looking for at least a 50% reduction in LDL-C or for them to reach their guideline-recommended LDL-C targets. So, if they're not there, I immediately add a non-statin lipid-lowering therapy and that's where shared decision-making comes into play. We start talking about their individual needs and preferences according to their lifestyle, etcetera, in the attempt to choose a therapy that will be a good fit for them and something that they will take.
And this is where LEQVIO comes in. Its HCP administered and dosed twice a year, after 2 initial injections. In my practice, patients typically come to see me once every 6 months anyway, so it's just one less thing that they have to worry about taking at home.
In addition, we know that LEQVIO has been shown in clinical trials to have proven efficacy with a well-tolerated safety profile. The potential for the efficacy seen in trials with HCP administration really excites my patients.
Viet:
I fully agree with you. Efficacy, tolerability, and adherence are what I look for in a therapy. And adherence is becoming even more of a focus of mine because even if a drug is proven to be effective, it only does its job if it’s taken as prescribed. The reality is that we do have patients in our clinics who are not where they should be with their LDL-C goals, despite being on maximally tolerated statins.
So, let’s dive deeper into why LEQVIO may be an option for these patients. Would you tell us more about LEQVIO clinical data and how it supports your choice of lipid-lowering therapy for LDL-C management in your patients with ASCVD or a recent coronary event?
Dr Saucier:
Of course. First, let me give you an overview of the pivotal trials. LEQVIO was studied in ORION-10 and ORION-11, multicenter, double-blind, randomized, placebo-controlled, 18-month, Phase 3 clinical trials in patients with established ASCVD or increased risk of cardiovascular disease (CVD).
Patients were taking a maximally tolerated statin with or without other lipid-modifying therapy and required additional LDL-C reduction. The primary efficacy measure was the percent change in LDL-C from baseline to Day 510.
Looking at results for ORION-10, we see LEQVIO demonstrated powerful and consistent LDL-C reduction throughout each 6-month dosing interval, with a 52% LDL-C reduction difference from placebo at Month 17 from baseline when administered in addition to maximally tolerated statin-based therapy.
And more than 80% of patients treated with LEQVIO achieved guideline-recommended LDL-C targets.
Results were similar in ORION-11 in patients with ASCVD or increased risk of CVD. And this is consistent with what I see in my clinical practice. We were actually the first site in Connecticut to initiate LEQVIO, and I have a large number of patients who have been very successful with getting their LDL-C levels to where they're supposed to be.
Viet, how do you talk to your patients about their therapy options?
Viet:
What ends up happening in my first consult with any patient, after taking them through the entire anatomy and physiology, is to then talk about where their LDL cholesterol should be. I like to do the math with them. I go through the 2022 Expert Consensus guidelines and talk with them about the goal of getting to guideline-recommended LDL-C targets and how we’re going to do that. I tell them that we’ll start with diet and statins and do a reassessment in 4 to 6 weeks. Patients are sometimes surprised when they start to see a change in their LDL cholesterol, and I’m like, trust the process!
If patients don’t reach their goal after 4 to 6 weeks, there are a few different therapy options to discuss, and it becomes a conversation about what fits best into their lifestyle while helping them remain adherent and lowering their LDL-C. This includes a conversation about side effects to ensure they continue with the lipid-lowering therapy.
The powerful and consistent efficacy of LEQVIO with just 2 HCP-administered doses a year after the 2 initial doses is one of the reasons I recommend adding LEQVIO to many of my patients who are not at LDL-C target on their statin therapy.
Stephanie, what safety data do you look for when evaluating treatment options?
Dr Saucier:
Thanks, Viet. I also hone in on the importance of the safety profile when discussing therapy options. I want to make sure that patients are going to tolerate their therapy, that they're not going to want to stop it because of side effects. And that’s one of the things I love about LEQVIO. It was well tolerated in Phase 3 clinical trials.
Let’s take a look at the data. The most common adverse events seen in the trials were injection site reaction, arthralgia, and bronchitis.
Adverse reactions leading to discontinuation occurred in 2.5% of patients treated with LEQVIO vs 1.9% of patients receiving placebo. Injection site reactions were the most common cause of discontinuation (LEQVIO 0.2% vs placebo 0%). All were localized, predominantly mild or occasionally moderate, and none were severe.
The safety profile was consistent across all subgroups, including elderly, mild-to-moderate hepatic impairment, and mild-to-severe renal impairment patient populations.
In addition to discussing clinical data, it’s also important that we talk to our patients about how they will take their medication. Viet, we’ve talked a little about LEQVIO dosing and administration. Can you tell us about how you approach conversations with your patients about starting LEQVIO?
Viet:
I begin my conversations with patients by telling them simply, LEQVIO is HCP administered along similar clinical follow-up timelines. LEQVIO is dosed every 6 months, and for many of my patients, we already have them coming in every 6 months or so. Patients get really excited to hear there is an option that seamlessly integrates into their health care routine.
I also like to discuss how LEQVIO works in the body. I explain there are receptors for LDL-C that clear LDL-C from the liver but that there is this protein PCSK9 that slows this process. LEQVIO is designed to selectively target the liver and prevents the production of PCSK9 protein, this allows more LDL receptors to remove circulating LDL-C. And even though it’s a medication that’s given every 6 months, after administration, it is selectively taken up by the liver, and plasma concentrations rapidly decline within 24 hours and are undetectable in the plasma within 48 hours. And this information really resonates with my patients.
Dr Saucier:
I completely agree. LEQVIO is a therapy many of my patients can really appreciate when it comes to choosing a non-statin lipid-lowering therapy. We have a program set up through our office where, when a patient is hospitalized, we can identify who are not at lipid goals despite their high-intensity statin. We then go through their chart and can start doing prior authorizations for LEQVIO while they're still hospitalized. That way, they can come out of the hospital, and we typically already have approval. They then can just come right into our office and get their injection, and we can keep going from there.
And this is great for me because either I or one of the nurses is administering it, which allows me to know that patients are getting their dose.
Viet:
I fully agree. LEQVIO dosing and administration has benefits for both me and my patients. When a patient has experienced a recent event despite being on statin treatment, they often need an additional non-statin therapy to reach their guideline-recommended LDL-C targets. For this patient, it can be overwhelming to be discharged with multiple treatments that they need to incorporate into their life on top of their statin treatment. The adjustment after an event can represent a major lifestyle change. And as you and I have both seen in practice, patients don’t always reach their LDL-C targets despite their best efforts.
In my experience, it’s nice to have an HCP-administered treatment option to add on that can help manage LDL-C effectively, and I know that the patient is receiving treatment. But as we’ve discussed, a treatment can be efficacious only if it is taken as prescribed. Can you tell us about the data on adherence with LEQVIO?
Dr Saucier:
Yes, LEQVIO does have real-world evidence on adherence and persistence from a retrospective, observational real-world study. This study evaluated 12-month adherence and persistence for newly initiated patients on LEQVIO, evolocumab, and alirocumab using data from KOMODO, an administrative claims database.
Adherence was defined as the proportion of days covered or PDC; fully adherent patients were defined as having a PDC of greater than or equal to 0.8. PDC calculates the proportion of days a patient has access to their prescribed medication over a defined period of interest, which was 12 months for this study.
Data show 79% of patients receiving LEQVIO were fully adherent at 12 months vs 56% of patients for either evolocumab or alirocumab.
Persistence was defined as patients on therapy for 12 months after index date with less than or equal to 90 days’ gap for LEQVIO and less than or equal to 60 days’ gap for evolocumab and alirocumab between last day of days’ supply and start of the next prescription.
And over 80% of patients were persistent on LEQVIO for 12 months after initiation vs 56% of patients on evolocumab and 57% of patients on alirocumab. However, the comparison pertains only to differences in adherence or persistence as defined by this analysis and should not be considered a comparison of efficacy or safety.
Given that this is an observational real-world study, there were some limitations, such as the study being conducted using administrative claims data, that is, collected for non-research purposes, with limited details on clinical variables and susceptibility to missing data and coding-related errors. Clinical characteristics and medications were captured during the 12 months prior to the initiation period; anything beyond the 12-month period was not observable.
LEQVIO is HCP administered. Therefore, claims ensure patients received the injection, whereas evolocumab and alirocumab claims do not confirm self-administration, so PDC for PCSK9 monoclonal antibodies may be overestimated.
Viet:
It’s fantastic to see these adherence data for LEQVIO vs PCSK9 monoclonal antibodies, and it aligns with what I am seeing with my patients. I especially like to see that persistence data because those are the patients who have continued with therapy.
Dr Saucier:
Thank you, Viet. I really enjoyed our discussion. But unfortunately, we're out of time.
On behalf of Viet and myself, thank you for taking the time to listen to our discussion on the importance of LDL-C management and empowering our patients through shared decision-making. We hope you found this program helpful for you in your practice.
References:
11/24 FA-11274277
Experts discuss the importance of LDL-C management after a coronary event and offer insights on real-world adherence for nonstatin lipid-lowering therapy.
Following a coronary event1, reaching and remaining at LDL-C target is critical. Join experts as they share their insights on adherence to LEQVIO® (inclisiran), a nonstatin lipid-lowering treatment option. Learn about the significance of shared decision making in ensuring patients start and stay committed to their lipid-lowering therapy.
Reference:
LEQVIO 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).1
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.1
Reference:
Novartis Pharmaceuticals Corporation 4/25 FA-11367461
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