To report the FDA approval of enlicitide (LIPFENDRA) for reducing LDL cholesterol in adults with hypercholesterolemia.
Approach:
Approval Details: Enlicitide is approved as an adjunct to diet and exercise for adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia.
Mechanism of Action: Enlicitide is a macrocyclic peptide that binds PCSK9, inhibiting its interaction with LDL receptors.
Clinical Trials: The approval was supported by phase 3 CORALreef Lipids and CORALreef HeFH trials, which were randomized, double-blind, and placebo-controlled.
Key Findings:
Enlicitide produced a 56% placebo-adjusted reduction in LDL-C at week 24 in CORALreef Lipids.
In CORALreef HeFH, enlicitide resulted in a 59% placebo-adjusted reduction in LDL-C at week 24.
Reductions in non–high-density lipoprotein cholesterol and apolipoprotein B were observed in both trials.
Adverse reactions were similar between enlicitide and placebo groups, with diarrhea and dizziness reported.
Interpretation:
Limitations:
The long-term effects on cardiovascular morbidity and mortality are still under investigation.
Conclusion:
Enlicitide is the first oral PCSK9 inhibitor approved by the FDA, providing a new option for LDL cholesterol management.
