By Fineline Cube 
US-based Merck, Sharp & Dohme Inc. (MSD; NYSE: MRK) disclosed encouraging topline results from the Phase 3 CORALreef Lipids trial, evaluating the once‑daily oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor enlicitide decanoate in adults with hypercholesterolemia who are on moderate‑ or high‑intensity statin therapy or who have documented statin intolerance.
Key Findings
- Efficacy – Enlicitide achieved a mean LDL‑C reduction of ~45 % versus placebo, meeting the primary endpoint of the study.
- Safety – The safety profile was consistent with that of other oral lipid‑lowering agents; the most common adverse events were mild gastrointestinal symptoms and transient headache.
- Population Impact – The drug demonstrated robust LDL‑C lowering in both statin‑tolerant and statin‑intolerant cohorts, indicating broad therapeutic potential.
Why Enlicitide Matters
| Feature | Significance |
|---|---|
| First‑in‑Class Oral PCSK9 Inhibitor | Offers the convenience of a daily pill versus the current injectable monoclonal antibodies. |
| Macrocyclic Peptide | Combines the potency of biologics with the oral bioavailability of small molecules. |
| Mechanism of Action | Binds directly to PCSK9, preventing its interaction with LDL receptors and increasing receptor recycling for enhanced LDL-C clearance. |
Strategic Implications
- Merck’s Portfolio – Enlicitide could become the flagship oral PCSK9 therapy, expanding Merck’s cardiovascular drug lineup and potentially capturing a significant share of the $30 billion PCSK9 market.
- Patient Benefit – Daily oral dosing may improve adherence and reduce injection‑related anxiety, addressing a key barrier to current PCSK9 treatments.
- Next Steps – Merck plans to submit a New‑Drug Application (NDA) to the FDA in 2026, contingent on confirmatory Phase 3 data and regulatory review.-Fineline Info & Tech