Merck's Enlicitide Decanoate Shows 40% LDL-C Reduction in Phase 3 Trials

Merck & Co., Inc. recently announced positive results from the first two of three Phase 3 clinical trials for its investigational oral PCSK9 inhibitor, enlicitide decanoate. The trials, named CORALreef HeFH and CORALreef AddOn, demonstrated significant efficacy in treating high cholesterol. The drug is designed for patients who are already undergoing lipid-lowering therapy, including the use of statin medications.

High cholesterol, characterized by elevated levels of low-density lipoprotein (LDL) cholesterol, is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). Despite dietary adjustments and statin therapy, many patients with high cholesterol fail to achieve or maintain the LDL-C reduction targets recommended by guidelines. The trials included patients with a history of ASCVD events or a high risk of ASCVD, who were undergoing moderate- or high-intensity statin treatment. Some patients were also using other lipid-lowering medications.

The primary endpoints of the trials included the average percentage change in LDL-C levels from baseline to week 24, the number of participants experiencing one or more adverse events (AEs), and the number of participants discontinuing the trial medication due to AEs. Secondary endpoints included the average percentage change in LDL-C from baseline to week 52, as well as changes in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and lipoprotein(a) at week 24.

The analysis showed that both the CORALreef HeFH and CORALreef AddOn trials successfully met their primary endpoints and all key secondary endpoints. The data indicated that enlicitide decanoate significantly improved LDL-C reduction compared to placebo (CORALreef HeFH) or other oral non-statin medications (CORALreef AddOn). Additionally, the incidence of AEs and serious adverse events (SAEs) in patients using enlicitide decanoate was clinically comparable to that of the control groups in both studies.

These findings are particularly noteworthy as they suggest that enlicitide decanoate could become the first orally administered PCSK9 inhibitor approved by the U.S. Food and Drug Administration (FDA). The development of an effective oral PCSK9 inhibitor could transform the treatment landscape for high cholesterol, offering a more convenient and accessible option compared to currently available injectable PCSK9 inhibitors.

The positive results from these trials underscore Merck's dedication to innovation in cardiovascular health. The company has been a leader in developing new therapies to address unmet medical needs, and the success of enlicitide decanoate in these trials is a testament to their ongoing efforts. As the pharmaceutical industry continues to advance, Merck's focus on developing patient-friendly treatments is likely to be well-received by healthcare providers and patients alike.