Merck's Enlicitide Cuts LDL Cholesterol by 60% in CORALreef Trials

Merck's oral PCSK9 inhibitor, Lipfendra (Enlicitide), has been shown to reduce LDL cholesterol by approximately 60% through 52 weeks in the CORALreef trials. This reduction was accompanied by ApoB lowering of more than 50%, according to Ann Marie Navar, MD, PhD, a lead investigator on the study.

ApoB captures every atherogenic particle, including LDL, very-low-density lipoprotein, and lipoprotein(a), making it a more important biomarker than LDL cholesterol. Enlicitide also lowers Lp(a) but at a modest rate compared to dedicated Lp(a) therapies, according to Navar.

The CORALreef trials involved two large phase 3 studies: HeFH and Lipids. The former evaluated patients with heterozygous familial hypercholesterolemia, while the latter enrolled patients with or at risk for atherosclerotic cardiovascular disease who were not at lipid goals. Enlicitide's effectiveness was compared to monoclonal antibodies evolocumab and alirocumab, which also lower LDL cholesterol more than inclisiran.

Enlicitide is taken first thing in the morning on an empty stomach, with a 30-minute waiting period before eating or drinking. It can be co-administered with other fasting medications like levothyroxine or oral semaglutide and with statins or ezetimibe as add-on therapy.

Navar is optimistic that enlicitide's lower wholesale acquisition cost will translate into lower copays for patients, but payer coverage remains unsettled. An oral option removes a real barrier for patients who refuse injections, according to Navar.