For many people living with high cholesterol, diet changes and daily statin therapy may not be enough to hit their target levels. A new experimental pill, however, could provide an additional option for those struggling to control their low-density lipoprotein (LDL), or “bad,” cholesterol.Recent Phase 3 trial data revealed that participants who took the investigational drug ‘enlicitide’ alongside their usual cholesterol-lowering treatment saw reductions in LDL cholesterol of up to 60% after 24 weeks. This was compared to participants who continued their standard therapy with a placebo. The study included adults with elevated LDL and either a history of major cardiovascular events or an increased risk of such events, as per CNN.The results, which have not yet appeared in a peer-reviewed journal, were shared at the American Heart Association’s Scientific Sessions.High LDL cholesterol contributes to plaque buildup in arteries, which can increase the risk of heart disease, which is the leading cause of death in the U.S., with a fatality occurring roughly every 34 seconds.New Daily Pill May Cut Bad Cholesterol By 60%Merck, the company behind enlicitide, intends to apply for FDA approval early next year, according to Dr. Puja Banka, associate vice president of clinical research and global clinical development.“We aimed to see what enlicitide could achieve on top of statins, because about 70% of patients on lipid-lowering therapy still don’t reach guideline-directed targets,” said Banka.When Statins Alone Are Not EnoughThe trial enrolled 2,912 adults, averaging 63 years old, who had previously suffered a heart attack or stroke or were at medium-to-high risk for one over the next decade. Data was collected across 14 countries between August 2023 and July 2025.All participants had elevated LDL levels despite at least 30 days on stable lipid-lowering therapy, mostly statins. About 97% were on statins, and 26% were taking another cholesterol-lowering medication. During the trial, some participants were given enlicitide once daily, while others received a placebo, as per CNN.Enlicitide belongs to a class of drugs called PCSK9 inhibitors, which work by helping the body clear LDL cholesterol from the bloodstream. Statins, by contrast, block a liver enzyme to increase LDL removal.“Because enlicitide works differently from statins, it’s expected to further lower LDL cholesterol when used in combination,” explained Dr. Kristin Newby, a cardiologist at Duke University School of Medicine, who was not involved in the trial.As per CNN, after 24 weeks, participants on enlicitide experienced sustained LDL reductions through 52 weeks, along with:A 53% drop in non-HDL cholesterolA 50% decrease in ApoB, a protein that carries harmful cholesterol in the bodyA 28% reduction in lipoprotein(a), a type of fat linked to heart diseaseSafety and Side EffectsAround 10% of participants on enlicitide experienced serious adverse events, compared with 12% in the placebo group. Side effects were generally balanced between both groups, with no particular event standing out. Reported issues included gastrointestinal symptoms and certain infections.“This suggests no major or frequent safety concerns,” said Newby, as per CNN. “However, larger, long-term studies and post-marketing surveillance will be needed to monitor for rarer side effects. The key takeaway is that enlicitide is highly effective at lowering LDL cholesterol—about 55% more than placebo when added to statins—and helps more people reach treatment goals.”A New Option for Cholesterol ManagementFor patients who don’t fully respond to statins, injectable PCSK9 inhibitors are already available. But unlike those treatments, enlicitide is an oral daily pill, offering an easier administration route that some patients may prefer. Banka called it “the first oral PCSK9 inhibitor to complete Phase 3 trials.”Previously, studies have shown that injectable PCSK9 inhibitors, like evolocumab (Repatha), can reduce the risk of first-time major cardiovascular events in adults with atherosclerotic cardiovascular disease or diabetes. In trials across 33 countries, 12,257 adults taking evolocumab for an average of 4.6 years saw a 25% reduction in heart attack, stroke, or coronary deaths compared with placebo. The FDA has already approved evolocumab for patients with established cardiovascular disease or as an add-on therapy for high cholesterol.The new enlicitide trial marks the first demonstration of a non-statin PCSK9 inhibitor improving cardiovascular outcomes in patients without a prior heart attack or stroke who were already on intensive lipid-lowering therapy.
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