Ann Marie Navar explains how enlicitide’s sustained LDL-C lowering, favorable tolerability, and structured dosing may improve adherence and expand oral add-on options for patients not at goal on statins.
In an interview with Pharmacy Times, Ann Marie Navar, MD, PhD, an associate professor of internal medicine and member of the Division of Cardiology at UT Southwestern Medical School and study investigator in the phase 3 CORALreef Lipids trial (NCT05952856), discussed longer-term efficacy, safety, and adherence findings for enlicitide (Merck & Co), an investigational oral proprotein convertase subtilisin/kexin type (PCSK9) inhibitor, and their relevance for clinical practice. Navar emphasized that the
Pharmacy Times: What stood out to you most in the final results of CORALreef Lipids that pharmacists should pay attention to when evaluating enlicitide’s real-world potential? And how might an oral PCSK9 inhibitor influence adherence patterns compared with both statins and injectable PCSK9 therapies?
Ann Marie Navar, MD, PhD: The final results are consistent with what we presented previously. The key findings are that even out to 1 year, those randomized to enlicitide had significant reductions in LDL-C and other atherogenic lipoproteins. Pharmacists will be essential in helping remind patients about how to take elicitide—first thing in the morning on an empty stomach, and it can be taken with other medications. I think this actually ended up being a benefit of the drug. By giving patients specific directions on how to take this, patients were able to make a routine out of taking it. I suspect that this actually translated to better adherence overall than had we been more vague and just told people to take it “once a day.” By the end of the study, participants reported high degrees of adherence to these instructions and to the drug in general.
Pharmacy Times: The study included patients already receiving background lipid-lowering therapy. How should pharmacists think about positioning enlicitide alongside statins, ezetimibe, or combination therapy in patients who remain above LDL-C goals?
Navar: Statins should remain first-line for lipid lowering. Enlicitide, if approved, will be another option for patients who need add-on therapy to get to their goal. Based on its efficacy, for those who need more than about a 20% LDL-C lowering, I think enlicitide will emerge as the best option for someone wanting oral therapy based on the efficacy of the drug. At the end of the day, unfortunately, in the United States, it’s the payers and pharmacy benefit managers who have a lot of influence on what we are actually able to prescribe. I’m hopeful that this drug is priced to be accessible and that payers don’t tie our hands in prescribing like they did in the early days of the monoclonal antibodies.
Pharmacy Times: From a safety and monitoring standpoint, what aspects of the trial data should pharmacists be prepared to discuss with prescribers and patients as this therapy moves closer to clinical use?
Navar: I’d emphasize that this drug is extremely well tolerated. The most important monitoring parameter is LDL-C to ensure patients are taking it as prescribed!
Despite having numerous effective therapies, the majority of patients at highest risk of heart attack and stroke are not meeting guideline goals. We have got to do better. - Ann Marie Navar, MD, PhD
Pharmacy Times: Looking beyond LDL-C lowering alone, how do you see therapies like enlicitide fitting into broader cardiovascular risk reduction strategies—and how can pharmacists help ensure patients derive maximum benefit?
Navar: We lower LDL-C to prevent heart attacks and strokes. We need to keep reminding our patients that cholesterol is the building block of atherosclerotic plaque that leads to heart attacks and strokes. Lowering LDL cholesterol is central to reducing the risk of heart attacks and strokes. It will be critical once enlicitide is rolled out that when it’s used in addition to statins, all of us in the health care team, including our pharmacy colleagues, emphasize the importance of continued adherence to statin therapy.
Pharmacy Times: Is there anything else that you would like to add?
Navar: We’ve got a major problem in both primary and secondary prevention: despite having numerous effective therapies, the majority of patients at highest risk of heart attack and stroke are not meeting guideline goals. We have got to do better. I’m hopeful that having even more options for LDL-C lowering can help us get there.
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