- Phase 3 CORALreef AddOn: enlicitide decanoate (oral PCSK9 inhibitor) reduced LDL‑C 64.6% at 8 weeks when added to background statins
- Enlicitide showed greater LDL‑C reductions versus bempedoic acid (−56.7%), ezetimibe (−36.0%) and bempedoic acid+ezetimibe (−28.1%) at day 56
- 78.2% of enlicitide patients achieved ≥50% LDL‑C reduction and LDL‑C <55 mg/dL versus 2.0%, 8.0% and 20.0% for bempedoic acid, ezetimibe and the combination
- FDA awarded enlicitide a Commissioner’s National Priority Voucher in December 2025; CORALreef Outcomes completed enrollment with >14,500 participants and the program includes >19,000 participants
Study design
CORALreef AddOn was a randomized, double‑blind Phase 3 trial comparing oral enlicitide decanoate to bempedoic acid, ezetimibe and their combination, added to background statins in adults with hypercholesterolemia and ASCVD or at risk for ASCVD; the primary endpoint was percent change in LDL‑C at week 8.
Primary efficacy
At eight weeks enlicitide reduced LDL‑C by 64.6% from baseline and showed greater reductions versus bempedoic acid (−56.7%), ezetimibe (−36.0%) and bempedoic acid+ezetimibe (−28.1%), all p<0.001.
Secondary endpoints and goal attainment
Enlicitide reduced apolipoprotein B by 54.6% and non‑HDL‑C by 58.0% from baseline (all p<0.001 versus comparators); lipoprotein(a) fell 26.2% with enlicitide versus increases or no change with comparators; 78.2% of enlicitide patients achieved ≥50% LDL‑C reduction and LDL‑C <55 mg/dL compared with 2.0%, 8.0% and 20.0% for bempedoic acid, ezetimibe and the combination, respectively.
Safety and program status
Safety was consistent with prior CORALreef trials with no clinically meaningful differences in adverse events and no drug‑related serious AEs or discontinuations for enlicitide; adherence was high (~98%). The FDA awarded a Commissioner’s National Priority Voucher (Dec 2025) and the CORALreef program encompasses over 19,000 participants, with CORALreef Outcomes having completed enrollment of more than 14,500 participants.
