J Am Coll Cardiol
Oral PCSK9 inhibitor enlicitide outperforms oral non‑statins in phase 3 trial
Clinical takeaway: For patients not at LDL‑C goal on statins who prefer oral therapy, enlicitide delivered substantially greater lipid lowering than current oral non‑statins and may shift add-on treatment choices pending outcomes data.
Despite widespread statin use, many patients with ASCVD or high CV risk fail to achieve guideline LDL‑C targets. Injectable PCSK9 therapies are effective but underused, in part due to administration burden. The phase 3 CORALreef AddOn trial evaluated whether a once-daily oral PCSK9 inhibitor could close this gap.
In this phase 3, randomized, double-blind, active-comparator trial of 301 statin-treated adults (mean age 64; 37% women), patients received enlicitide 20 mg or oral comparators—bempedoic acid, ezetimibe, or their combination—for 56 days. Baseline LDL‑C averaged ~92 mg/dL. At day 56, enlicitide reduced LDL‑C by ~65%, compared with ~28% with ezetimibe, ~6% with bempedoic acid, and ~37% with combination therapy (all P<0.001). Enlicitide also produced larger reductions in apoB and non–HDL‑C, with consistent effects across subgroups. Treatment-emergent adverse events and discontinuations (~2–4%) were similar between groups.
“Enlicitide showed superior efficacy in lowering LDL‑C, as well as apoB and non–HDL‑C, compared with currently approved oral add‑on agents,” the authors wrote, noting its potential role for patients who need lipid lowering beyond statins.
Source: Catapano AL, et al; CORALreef AddOn Investigators. (2026, March 30). J Am Coll Cardiol. Oral PCSK9 Inhibitor Enlicitide versus Oral Non-statin Therapies: A Phase 3 Randomized Clinical Trial