Enlicitide plus statins shows positive lipid-lowering effects

Enlicitide, as an add-on therapy to statins, demonstrated a significant reduction in low-density lipoprotein cholesterol (LDL-C) compared with other lipid-lowering therapies in patients with hypercholesterolaemia, according to phase 3 data reported by Prof. Alberico L. Catapano (University of Milan, Italy) [1].

CORALreef AddOn (NCT06450366) was a phase 3, randomised, controlled trial in patients with either a history of major atherosclerotic cardiovascular events and LDL-C levels ≥55 mg/dL, or those at risk for such events with LDL-C levels ≥70 mg/dL. Patients were randomised in a 2:1:1:2 ratio to receive enlicitide, bempedoic acid, ezetimibe, or bempedoic acid plus ezetimibe for 56 days. All treatment groups received background statin or other lipid-lowering therapies, with no planned changes during the trial. The primary endpoint was the percentage change in LDL-C at day 56. In total, 301 patients were included.

The trial met its primary endpoint, demonstrating a significantly greater reduction in LDL-C with enlicitide compared with all 3 groups at day 56, with the largest effect observed versus bempedoic acid monotherapy. Additionally, enlicitide led to significant improvements in non-HDL-C, apolipoprotein B (ApoB) and lipoprotein(a) (Lp(a)) compared with the other treatment arms. The incidence of adverse events was generally balanced across groups. No serious adverse events or discontinuations due to drug-related adverse events were reported with enlicitide.

“We observed a rapid, robust reduction in LDL-C, with a mean decrease of up to 64.6%, and a significant LDL-C reduction compared with bempedoic acid, ezetimibe, or their combination,” concluded Prof. Catapano. “As an easy-to-use oral add-on therapy, enlicitide may help close the gaps in lipid management by enabling rapid and substantial LDL-C lowering in at-risk patients not at goal on statin therapy, and support efforts to address the ongoing cardiovascular disease burden.”

Catapano AL, et al. Efficacy and safety of enlicitide decanoate, an oral macrocyclic peptide inhibitor of PCSK9, compared with bempedoic acid, ezetimibe, or bempedoic acid co-administered with ezetimibe in statin-treated adults with hypercholesterolemia: Phase 3 CORALreef AddOn trial. ACC 2026, 28–30 March, New Orleans, LA, USA.