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Oral PCSK9 Inhibitor Shows Promise in Lowering LDL-C
In the randomized, double-blind, placebo-controlled, phase 3 coralreef Lipids (NCT05952856) clinical trial, enlicitide decanoate, an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, demonstrated notable and clinically meaningful reductions in low-density lipoprotein cholesterol (LDL-C). The study focused on the safety, efficacy, and tolerability of the treatment among individuals with hypercholesterolemia on a moderate- or high-intensity statin.1,2
Clogged arteries, Cholesterol plaque in artery. 3d illustration – Image credit: Rasi | stock.adobe.com
“This is the third phase 3 trial to demonstrate clinically meaningful and statistically significant LDL-C lowering for enlicitide,” Dean Y. Li, MD, PhD, president of Merck research laboratories, said in a news release. “The advent of injectable PCSK9 inhibitors has enabled a new approach to controlling LDL-C and reducing the risk of atherogenic cardiovascular events.”1
Understanding Hypercholesterolemia & enlicitide
Hypercholesterolemia is a disorder that induces high levels of LDL-C in the blood, which causes fat to build up in the arteries. this buildup increases an individualS risk for heart attack, stroke, and atherosclerosis, which is the leading cause of cardiovascular disease. Additionally, hypercholesterolemia impacts nearly 86 million US adults and accounts for 85% of cardiovascular deaths.1,3
Enlicitide can offer further treatment options for hypercholesterolemia as the potential first oral PCSK9 inhibitor designed to lower LDL-C using the same biological mechanism as approved monoclonal antibody-based injectable PCSK9 inhibitors. As a novel small molecule peptide, enlicitide binds to PCSK9 and inhibits the interactions of PCSK9 with LDL receptors, according to the study authors.1
“Enlicitide,designed to deliver PCSK9 inhibition through a convenient oral route,has the potential to significantly expand access to this vital therapy,” Li added.1
The CORALreef Lipids trial included 1561 participants with hypercholesterolemia who were already taking statin therapy. Participants were randomly assigned to recieve either 60 mg of enlicitide decanoate or a placebo once daily for 12 weeks. The results showed that enlicitide decanoate reduced LDL-C levels by 55.9% compared to a 14.3% reduction with placebo (P < .001).1
The moast common adverse events reported in the enlicitide decanoate group were nasopharyngitis, headache, and elevations in liver enzymes. These events were generally mild and manageable, according to the researchers.1
Further research is ongoing to evaluate the long-term safety and efficacy of enlicitide decanoate, as well as its potential to reduce cardiovascular events. The findings from the CORALreef Lipids trial represent a significant step forward in the treatment of hypercholesterolemia and offer hope for a more convenient and accessible therapy for patients at risk of cardiovascular disease.1