MSD has announced receipt regulatory approval in its US homeland for Lipfendra (enlicitide), an oral macrocyclic peptide PCSK9 inhibitor, for reducing low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolaemia, including heterozygous familial hypercholesterolaemia (HeFH). This marks the first oral PCSK9 inhibitor approved in the country, offering a daily oral alternative to existing injectable antibodies and siRNA therapies.

The approval was supported by three Phase III CORALreef studies demonstrating statistically significant LDL-C reductions of 57.1% to 64.6% versus placebo or other oral non-statin agents, with a consistent safety profile.

Enlicitide works by selectively binding PCSK9 to prevent its interaction with LDL receptors, thereby restoring clearance capacity without compromising haemostasis. While the current approval is based on lipid-lowering efficacy rather than cardiovascular outcomes, the ongoing CORALreef Outcomes trial is designed to assess whether this potent reduction translates into fewer major adverse cardiovascular events.