Oral PCSK9 Inhibitor Enlicitide Matches Injectables in Lowering LDL Cholesterol
Enlicitide: A Promising Oral PCSK9 Inhibitor – Key Takeaways
this article details the results of the phase 3 CORALreef lipids trial for enlicitide, a new oral PCSK9 inhibitor aiming to lower LDL cholesterol in adults with or at risk for atherosclerotic cardiovascular disease (ASCVD). Here’s a summary of the key findings:
Efficacy:
* Significant LDL-C Reduction: Enlicitide demonstrated a ample reduction in LDL-C. After excluding biologically implausible values, the reduction was 59.7% at 24 weeks and 52.4% at 52 weeks.
* Consistent lowering: A chart presented at AHA 2025 showed a clear and consistent drop in mean LDL-C with treatment.
* Impact on Other Lipids: Enlicitide also considerably lowered:
* Non-high-density lipoprotein cholesterol: 53% reduction
* Apolipoprotein B: 50% reduction
* Lipoprotein(a): 28% reduction
* Treatment Goals Achieved: Nearly 70% of participants achieved both at least a 50% LDL-C reduction and an LDL-C below 70 mg/dL. Over two-thirds reached levels below 55 mg/dL.
* Comparable to Inclisiran: Results were reported as being numerically better than those seen with inclisiran (an siRNA medication).
Safety & Tolerability:
* Comparable to Placebo: The safety profile of enlicitide was similar to placebo.
* Adverse events: AEs occurred in 64% of enlicitide patients vs.62% of placebo patients. Serious AEs were reported in 10% and 12% respectively.
* Discontinuation Rate: Only 100 patients total discontinued treatment due to AEs.
* Mortality: deaths occurred in 0.7% of each group.
* No New Safety Signals: No unexpected safety concerns were identified.
Future Outlook:
* The CORALreef outcomes trial is ongoing to determine if the LDL-C lowering effects of enlicitide translate into a reduction in major cardiovascular events.
Source: Presented at AHA 2025 Scientific Sessions; november 8, 2025; New Orleans, LA. https://newsroom.heart.org/news/investigational-daily-pill-lowered-bad-cholesterol-as-much-as-injectables