Enlicitide Decanoate

  Product Detail  

1. Chemical Profile

• Compound Class: Orally bioavailable macrocyclic 8-amino-acid synthetic peptide PCSK9 inhibitor
• Mechanism of Action: Selectively binds circulating PCSK9 protein, blocks PCSK9-LDL receptor (LDLR) protein-protein interaction. Restores hepatic LDLR recycling to accelerate liver clearance of LDL-C, Lp(a), non-HDL-C and apoB lipoproteinsMerck.
• Key Advantage: First oral PCSK9 inhibitor; all prior PCSK9 agents are injectable monoclonal antibodies.

2. FDA Approval Information

• Approval Date: July 16, 2026 (U.S. FDA)Merck
• Marketing Company: Merck & Co. (MSD outside US/Canada)
• Approved Strength: 20 mg oral tablet (only marketed dosage)
• Official Indication: Adjunct to diet and exercise to reduce LDL-C in adult patients with:
  1. Primary hypercholesterolemia
  2. Heterozygous Familial Hypercholesterolemia (HeFH)
  3. Atherosclerotic cardiovascular disease (ASCVD) on statin background therapy
• Administration Instruction: Once daily, fasting state (no food 2 hours before and after dosing); food drastically reduces oral bioavailability. Swallow whole tablet, do not split or crush.

3. Clinical Efficacy (CORALreef Phase 3 Global Trials)

• Fixed 20 mg once-daily regimen used in all registration trials.
• When added to statin therapy, mean LDL-C reduction reached ~64.6% at week 8 vs baseline.
• Secondary lipid endpoints: Significant lowering of lipoprotein(a), apolipoprotein B and non-HDL cholesterol.
• No dose titration required; 20 mg is the sole approved maintenance dose for all eligible populations.

4. Pharmacokinetics Highlights

• Terminal half-life: ~24 hours, supporting once-daily oral dosing
• Food effect: High-fat meal reduces systemic exposure by ~67% (strict fasting mandate in label)
• Linear exposure across 6 mg–30 mg oral doses; 20 mg selected for optimal efficacy/safety balance
• Low systemic immunogenicity risk vs injectable PCSK9 mAbs

5. Safety Profile

• Nausea, diarrhea, abdominal discomfort, constipation
• Mild transient gastrointestinal events generally resolve within 4 weeks of continuous dosing
  
  
  No severe liver or muscle toxicity signals observed in Phase 3 program; no routine LFT/CK monitoring required.

6. Commercial Differentiation

• First and only oral PCSK9 inhibitor globally
• Lower monthly acquisition cost vs injectable PCSK9 antibodies
• Improves patient medication adherence by eliminating subcutaneous injection requirements
• Compatible with statins, ezetimibe and other lipid-lowering agents without dose adjustment

7. Regulatory Application Scenarios for CAS 2861205-06-1

• DMF, ANDA, IND, patent filing with FDA/EMA/KFDA/CDE
• API import & export customs documentation
• GMP raw material quality control, COA and impurity profiling
• Distinction from injectable PCSK9 biologics (evolocumab, alirocumab) and other oral lipid agents