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Oral PCSK9 Pill Enlicitide Cuts LDL by Up to 60% in Phase 3

Merck targets an FDA filing next year pending outcomes data.

Overview

  • In the CORALreef Lipids Phase 3 trial, once-daily enlicitide added to background therapy lowered LDL cholesterol by as much as 60% versus placebo at 24 weeks, with reductions sustained through 52 weeks.
  • Participants also saw a 53% drop in non‑HDL cholesterol, a 50% decrease in ApoB, and a 28% reduction in lipoprotein(a) compared with placebo.
  • The study enrolled 2,912 adults across 168 sites in 14 countries (mean age 63), most with prior events or elevated risk, with 97% already on statins.
  • Serious adverse events occurred at similar rates with enlicitide and placebo (about 10% vs 12%), and discontinuations due to side effects were low (3% vs 4%).
  • Investigators reported LDL and related lipid reductions comparable to injectable antibodies alirocumab and evolocumab and numerically greater than inclisiran, while noting that the AHA presentation is preliminary and a separate outcomes trial is still underway.