Researchers reported Wednesday that Merck’s experimental cholesterol-lowering pill enlicitide sharply reduced LDL cholesterol in people who remained at high risk of heart attacks despite taking statins. The report, published in the New England Journal of Medicine, described enlicitide as an experimental alternative to injected medicines that lower cholesterol by targeting a liver protein called PCSK9. If approved by the Food and Drug Administration, the pill could offer an easier-to-use option for millions of people, the researchers said.
Statins, which block part of the liver’s production of cholesterol, are a cornerstone of treatment, the researchers noted, but they do not bring many patients to recommended LDL goals. In the study, more than 2,900 high-risk patients were randomly assigned to add a daily enlicitide pill or a dummy drug to their existing standard therapy, according to the report. Over six months, enlicitide users saw their LDL cholesterol drop by as much as 60%, researchers reported.
The LDL reductions persisted over time, with the benefit dropping only slightly over the following year, the researchers said. The report also found no safety difference between patients taking enlicitide and those taking placebo. One practical caveat, however, was that the pill must be taken on an empty stomach.
The study’s findings were framed against the current cholesterol options for people who need additional LDL lowering beyond statins. The report noted that while some added pills exist, none “come close to the degree of LDL cholesterol lowering that we see with enlicitide,” said study lead author Dr. Ann Marie Navar, a cardiologist at UT Southwestern Medical Center.
The report also described how PCSK9 inhibitor injections work differently from pills. Rather than targeting cholesterol production in the liver like statins do, the injected drugs block PCSK9, a protein that limits the body’s ability to clear cholesterol from blood. It said only a small fraction of people who could benefit from PCSK9 inhibitors use them and that even as shot prices have dropped recently, patients may not want to administer injections and doctors may find them more complex to prescribe. It added that Merck funded the enlicitide study and that the FDA has added the drug to a program promising ultra-fast reviews.
In an accompanying journal perspective, Dr. William Boden of Boston University and the VA New England Healthcare System, who said he was not involved with the study, wrote that it provides “compelling evidence” that the pill lowers cholesterol about as much as PCSK9 shots. Boden, however, cautioned that the study does not yet show whether lowering LDL cholesterol with enlicitide leads to fewer heart attacks, strokes and deaths, saying that would take much longer to prove. The report said Merck has a study of more than 14,000 patients underway to answer that question.