Results from a late-stage clinical trial published today in the Modern England Journal of Medicine demonstrate that the investigational drug enlicitide significantly lowers low-density lipoprotein cholesterol (LDL-C) in patients at risk for atherosclerotic cardiovascular disease (ASCVD) events.
The double-blind, placebo-controlled trial involved 1,584 participants with a history of, or at high risk for, ASCVD. Participants were randomized to receive either enlicitide or a placebo, in addition to standard-of-care lipid-lowering therapy, for 24 weeks. The primary endpoint was the percentage change in LDL-C from baseline to week 24.
The study found that enlicitide resulted in a statistically significant reduction in LDL-C compared to placebo. Specifically, patients receiving enlicitide experienced a 38% reduction in LDL-C levels, while those receiving placebo experienced a 7% reduction. The difference between the two groups was statistically significant (P < 0.001). Researchers noted the magnitude of LDL-C reduction was consistent across pre-specified subgroups, including those with varying baseline LDL-C levels and those receiving different statin therapies.
Enlicitide functions by inhibiting the enzyme PCSK9, a protein that regulates the number of LDL receptors on liver cells. By inhibiting PCSK9, enlicitide increases the number of LDL receptors, leading to greater clearance of LDL-C from the bloodstream. Existing PCSK9 inhibitors are available, but enlicitide is administered orally, offering a potential advantage over currently available injectable therapies.
The trial also assessed the safety and tolerability of enlicitide. The drug was generally well-tolerated, with adverse events similar to those observed with placebo. The most common adverse events reported in the enlicitide group were nasopharyngitis, headache, and muscle pain, but these occurred at similar rates to the placebo group. Serious adverse events were rare and did not differ significantly between the two groups.
The findings come as public health officials continue to monitor the efficacy of updated COVID-19 vaccines. Recent data from the Veterans Affairs system suggest that the 2024-25 COVID vaccine offers between 29% and 64% efficacy against poor outcomes, according to a report published by CIDRAP on February 9, 2026.
Researchers are preparing to present further analysis of the enlicitide trial data at upcoming cardiology conferences. The pharmaceutical company developing enlicitide has indicated its intention to submit a New Drug Application to the Food and Drug Administration in the coming months. The FDA has not yet announced a timeline for review.
