N Engl J Med
Oral PCSK9 inhibitor shows potent LDL lowering in phase 3 trial
The phase 3 CORALreef Lipids trial (NCT05952856) demonstrated that daily oral enlicitide produced substantial LDL‑C reductions in adults with established or at‑risk ASCVD. In this 2,909‑participant study, enlicitide achieved a 57% mean LDL‑C reduction at 24 weeks, compared with a 3% increase with placebo, for an adjusted between‑group difference of nearly 56 percentage points. Improvements in non‑HDL‑C, apolipoprotein B, and lipoprotein(a) were also significantly greater with enlicitide, with safety outcomes similar to placebo.
Clinical takeaway: Pending regulatory approval, enlicitide may offer clinicians a potent, convenient oral option to help high‑risk patients reach LDL‑C goals when statins alone are insufficient.
Source:
Navar AM, et al; CORALreef Lipids Investigators. (2026, February 4). N Engl J Med. A Placebo-Controlled Trial of the Oral PCSK9 Inhibitor Enlicitide. https://www.nejm.org/doi/full/10.1056/NEJMoa2511002