New pill lowers cholesterol for patients already on statins— ...

An oral PCSK9 inhibitor is associated with significant reductions in low-density lipoprotein (LDL) cholesterol, according to new data presented at the American Heart Association’s Scientific Sessions 2025 conference. The PCSK9 inhibitors currently available on the market are all injectable. A PCSK9 inhibitor that does not require needles could be a potential game-changer in the field of preventive medicine. 

The CORALreef Lipids trial included nearly 3,000 heart patients with high LDL cholesterol. All participants were either already on statins or were known to be intolerant to statins. The group was randomized by a 2-to-1 ratio to either receive enlicitide decanoate, a new oral PCSK9 inhibitor from Merck, or a placebo for 24 weeks. All data were collected from August 2023 to July 2025 from sites in 14 different countries

Overall, enlicitide decanoate was linked to a reduction in LDL cholesterol of up to 60%, a 50% reduction in apolipoprotein B (ApoB) and a 28% reduction in lipoprotein(a). From a safety perspective, major side effects occurred at comparable rates in the two groups. 

“This oral medication is set to be another powerful addition to the treatments we currently have to lower LDL cholesterol and hopefully prevent cardiovascular events,” lead author Ann Marie Navar, MD, PhD, an associate professor of cardiology at the University of Texas Southwestern Medical Center in Dallas, said in a statement. “Many patients struggle to reach guideline-recommended cholesterol targets despite currently available therapies, leaving them at unnecessary risk of stroke and/or heart attack.”

Navar emphasized that these benefits were similar to what is typically seen with injectable PCSK9 inhibitors, providing patients with an alternative therapy that does not require the use of needles.

Merck plans on submitting data from CORALreef Lipids and two additional studies—CORALreef HeHF and CORALreef AddOn—to the U.S. Food and Drug Administration and other regulatory bodies around the world. 

“Enlicitide, if approved, adds to physicians’ armamentarium to lower LDL cholesterol,” Dean Y. Li, PhD, president of Merck Research Laboratories, said in a separate statement. “This moment is the result of Merck’s legacy and commitment to researching ways to help improve atherosclerotic cardiovascular disease outcomes for millions worldwide and our strength in medicinal chemistry using our novel macrocyclic peptide platform. Cardiovascular disease is the leading cause of death globally, and we look forward to bringing a potential new option to help address the cardiovascular epidemic.”

Click here for additional details about the American Heart Association’s Scientific Sessions 2025 conference.