New Pill Cuts “Bad” Cholesterol by 60%—A Potential Game Changer in Heart Disease Prevention
A new experimental pill, enlicitide, is showing remarkable promise in the fight against heart disease. In a phase three clinical trial published in The New England Journal of Medicine, enlicitide dramatically lowered levels of low-density lipoprotein (LDL) cholesterol – often referred to as “bad” cholesterol – by as much as 60%. If approved by the Food and Drug Administration (FDA), this oral medication could offer millions of Americans a new way to reduce their risk of heart attacks and strokes.
The Challenge of Lowering LDL Cholesterol
For decades, scientists have understood the central role LDL cholesterol plays in cardiovascular disease. These cholesterol particles accumulate inside artery walls in a process called atherosclerosis, potentially blocking blood flow and leading to heart attacks or strokes. Reducing LDL cholesterol is therefore a key strategy for both preventing heart disease and lowering risk in those already diagnosed. However, fewer than half of patients with established atherosclerotic cardiovascular disease currently reach recommended LDL cholesterol goals 1.
Building on Decades of Research
Enlicitide’s development builds on groundbreaking research conducted at UT Southwestern Medical Center. In 1985, Michael Brown, M.D., and Joseph Goldstein, M.D., were awarded the Nobel Prize in Physiology or Medicine for identifying the LDL receptor on liver cells, which helps remove LDL cholesterol from the bloodstream. This discovery paved the way for statins, the most widely used cholesterol-lowering drugs today. Further research at UTSW, led by Helen Hobbs, M.D., and Jonathan Cohen, Ph.D., revealed that genetic variations reducing production of the PCSK9 protein naturally lower LDL cholesterol. This insight led to the development of injectable PCSK9 inhibitors, such as evolocumab and alirocumab, which can likewise lower LDL cholesterol by about 60% 1.
Why Existing Treatments Aren’t Always Used
Even as injectable PCSK9 inhibitors are highly effective, their use in routine care has been limited. Initial barriers included high costs and insurance coverage issues. Even as those issues improve, many physicians remain hesitant to prescribe them, largely because these medications require injections rather than being taken as a pill 1.
How Enlicitide Works
Enlicitide targets the same PCSK9 pathway as injectable drugs, attaching to the protein in the bloodstream to enhance the body’s ability to remove LDL cholesterol. The key advantage of enlicitide is its oral administration – a once-daily pill – making it a potentially simpler and more convenient option for patients 2.
Phase Three Trial Results
The phase three clinical trial involved 2,909 participants with atherosclerosis or at risk due to related health conditions. Approximately two-thirds received enlicitide, while the remainder received a placebo. Most participants were already taking statins, yet their average LDL cholesterol level remained 96 milligrams per deciliter (mg/dl), exceeding recommended targets of 70 mg/dl for those with atherosclerosis and 55 mg/dl for those at risk of atherosclerotic cardiovascular disease.
After 24 weeks, patients taking enlicitide experienced an approximately 60% reduction in LDL cholesterol compared to those on the placebo. The drug also lowered other cardiovascular risk markers, including non-HDL lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a). These improvements were sustained over a year of follow-up 2.
“These reductions in LDL cholesterol are the most we have ever achieved with an oral drug by far since the development of statins,” said Ann Marie Navar, M.D., Ph.D., a cardiologist and Associate Professor of Internal Medicine at UT Southwestern Medical Center 2.
What’s Next?
A further clinical trial is currently underway to determine whether these cholesterol reductions will translate into a decreased incidence of heart attacks and strokes. The study was sponsored by Merck & Co. Inc. 1.