Enlicitide: A Welcome Addition to Lipid-Lowering Therapy

Mikhail N

Published on: 1970-01-01

Abstract

Enlicitide is an orally administered proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor under investigation in phase 3 clinical trials.  In the largest enlicitide trial (CORALreef) including patients with established or at high-risk of developing cardiovascular disease (CVD) already on statins, the changes in low-density lipoproptein cholesterol (LDL-C) levels after 24 weeks were -57.1% and 3.0% with enlicitide and placebo, respectively. Enlicitide decreased levels of the atherogenic non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B) and lipoprotein a [Lp(a)]; difference from placebo -53.4%, -50.3%, and -28.2%, respectively. Similar results were obtained in another phase 3 clinical trial of patients with heterozygous familial hypercholesterolemia (HeFH). In a third randomized trial lasting only 56 days, enlicitide was more effective than ezetimibe, bempedoic acid, and ezetimibe + bempedoic acid in decreasing LDL-C levels with reductions of -64.6%, -27.8%, -6.3%, and -36.5% versus baseline, respectively. Enlicitide was well tolerated for up to 1 year of use, with adverse effects and drug discontinuation rates comparable to placebo.  Enlicitide is a promising addition to lipid lowering therapy due to its ease of administration orally coupled with high efficacy and safety. Further studies are needed to examine long-term safety of enlicitide and its impact on CV outcomes and mortality.