Merck’s Oral PCSK9 Inhibitor Cuts LDL-C in Phase 3 Trial

Merck has made a significant advancement in cardiovascular disease treatment with the announcement of positive results from its Phase 3 CORALreef Lipids trial. The investigational drug, enlicitide decanoate, represents a groundbreaking approach as an oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor designed to lower low-density lipoprotein cholesterol (LDL-C).

Overview of the CORALreef Lipids Trial

The CORALreef Lipids trial, which enrolled 2,912 adults with or at risk for atherosclerotic cardiovascular disease (ASCVD), showcased the effectiveness of enlicitide. Participants were required to be on other lipid-lowering therapies or have documented statin intolerance.

• Participants: 2,912
• Treatment: 20 mg of once-daily oral enlicitide (1,942 participants) versus placebo (970 participants)
• Duration: 24 weeks for primary endpoint analysis; continued monitoring through 52 weeks

At the primary endpoint of 24 weeks, enlicitide demonstrated a statistically significant reduction in LDL-C of 55.8%. This reduction persisted with sustained effects observed at 52 weeks, including a 47.6% drop in LDL-C levels.

Key Findings

The results highlighted not only the primary LDL-C reductions but also secondary endpoints including:

• Non-high-density lipoprotein cholesterol (non-HDL-C)
• Apolipoprotein B (ApoB)
• Lipoprotein(a) (Lp(a))

The safety profile of enlicitide was comparable to that of the placebo group, indicating no significant difference in the occurrence of adverse events. Treatment adherence was notably high across all study groups, with 97% of participants following the dosing instructions.

Expert Insights

Dr. Ann Marie Navar, a lead author on the study, emphasized the transformative potential of enlicitide. Despite existing treatments, many patients with ASCVD still do not achieve their LDL-C goals. Enlicitide could be the solution to bridging this gap.

Dr. Dean Y. Li, president of Merck Research Laboratories, remarked on the essential nature of this oral treatment, stating it could expand the options available to healthcare providers in managing LDL-C levels.

Future Developments and Implications

Merck plans to present further data from the CORALreef Lipids trial to regulatory authorities globally. This trial is part of a larger effort evaluating enlicitide’s performance across multiple studies, involving over 19,000 participants with hypercholesterolemia.

Cardiovascular disease continues to be a significant health challenge globally. With around 18 million deaths annually attributed to cardiovascular issues, effective treatments like enlicitide are crucial in combatting this epidemic.

Enlicitide aims to provide a new, effective, and convenient oral alternative to existing lipid-lowering therapies, which may greatly enhance treatment options for patients and healthcare providers alike.