Efficacy and Equity With Oral PCSK9s: Ann Marie Navar, MD, PhD

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The first potential oral PCSK9 inhibitor not only offers similar efficacy to the current standard injectable PCSK9s available but also improved patient adherence and a potential to address existing inequities in access to non-statin lipid-lowering therapy, explained Ann Marie Navar, MD, PhD, associate professor in the departments of internal medicine and population and data sciences at UT Southwestern Medical Center.

Navar presented the results of the phase 3 CORALreef Lipids trial, evaluating the oral PCSK9 inhibitor enlicitide in adult patients with or at risk for atherosclerotic cardiovascular disease, at the 2025 American Heart Association Scientific Sessions, held in New Orleans, Louisiana, November 7-10, 2025.

The reduction in low-density lipoprotein (LDL) cholesterol seen at week 24 was exceptionally strong, she noted, rivaling the performance of established injectable monoclonal antibodies evolocumab (Repatha; Amgen) and alirocumab (Praluent; Regeneron). In the reanalysis of data at week 24, there was a 60% reduction in LDL cholesterol compared with placebo, which Navar called “a remarkable reduction.”

More than two-thirds of patients achieved at least a 50% reduction in LDL cholesterol and reached an on-treatment LDL cholesterol level of less than 55 mg/dL. Navar said it was “almost remarkable” how similar the reductions in LDL cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) were between the oral PCSK9 and the injectables.

“But it's actually not surprising, because the way that enlicitide works is very similar to how the monoclonals work,” she added.

The oral formulation adds a convenience over the injectables, with 97% of patients staying adherent to the prescribed dosing regimen. Not only does the addition of an oral pill offer patients more choice, but it also increases access to non-statin lipid-lowering therapy.

“My hope for enlicitide is that as an oral pill that's very easy to prescribe, that we may actually be able to increase the pool of clinicians that are adding on therapy after statins, and that is going to be a rising tide that lifts all boats and hopefully also helps equalize some of the inequity and access to non-statin lipid-lowering therapy that we're seeing now,” Navar said.