A powerful new drug from Merck – which introduced statins to the world nearly 40 years ago – could slash levels of dangerous LDL cholesterol to levels almost never seen in adults, reports The New York Times.
The pill, enlicitide, blocks a liver protein called PCSK9 that slows the body’s ability to clear cholesterol. With most PCSK9 blocked, LDL levels plummet and rates of heart attacks and strokes in high risk patients fall by up to 20% in just the first year.
Merck’s head of research said the goal is to make the pill affordable, and an alternative to expensive bi-weekly or monthly injections of monoclonal antibodies that do the same thing.
But only around 1% of eligible patients take the injections, which include Praluent by Regeneron and Sanofi, and Repatha by Amgen. Many patients don’t want to inject themselves, and insurers put up obstacles to paying, cardiologists say.
The drugs’ list prices are more than $500 a month.
At a recent American Heart Association meeting in New Orleans, Merck reported the results of a 24-week study of 2 912 people who had had a heart attack, stroke or other cardiovascular event, or were at risk for one. They were randomly assigned to take enlicitide, or a placebo.
Those taking enlicitide reduced their LDL levels by up to 60%, the same amount as achieved by the injections.
There was no difference in side effects between those taking the pill and those taking a placebo.
The company also reported results of a smaller study involving people with a genetic condition, familial hypercholesterolemia, that results in high LDL levels.
Multiple studies over the years have shown that the lower the LDL level, the better – heart attack and stroke rates drop as LDL levels fall. And there appears to be no downside to having an astonishingly low LDL level, including one in the teens or 20s.
Adults who are not taking cholesterol-lowering drugs usually have levels above 100.
When the injected drugs were approved a decade ago, it seemed that the PCSK9 protein could be “an obvious target” for a pill, said Dr Christie Ballantyne, a lead investigator for the Merck clinical trials and director of the Centre for Cardiometabolic Disease Prevention at Baylor College of Medicine in Texas.
But, Ballantyne said, chemists told him it was impossible.
The problem was that to block PCSK9, chemists would need to find a substance that would attach to the same large flat surface on the PCSK9 protein that antibodies in injectable drugs attach to. At cellular scales, antibodies are huge. A small molecule, like those in most pills, would be much too small.
The solution for Merck, after 10 years of research, was to make a circle of peptides, a one-hundredth the size of an antibody but larger than a typical pill-delivered small molecule.
That method, said Dr Dean Li, President of Merck Research Laboratories, could allow researchers to make pills that could replace many other injectable drugs.
Li noted that it is much cheaper to manufacture and transport pills than injectables, which have to be kept refrigerated. He said the goal is to keep the price of the PCSK9 pill low so it can be widely used in the United States and elsewhere.
He wants patients to view taking a PCSK9 pill as “no different from taking aspirin” or, he said, than a standard blood pressure drug.
“The dream is to democratise PCSK9,” he said. “This dream has the possibility of coming true.”
An affordable daily pill that has the same effect as the injected drugs could be transformative, said Dr Christopher Cannon, a cardiologist at Brigham and Women's Hospital in Boston who consults for several drug companies, but not Merck.
Dr David Maron, a preventive cardiologist at Stanford, said: “If they price this so that people can afford it, it will make a huge difference for the millions at risk for heart attacks and strokes. This is a really important advance.”
AstraZeneca is also working on a PCSK9 pill, said Maron, who is part of an independent expert group that monitors that drug’s safety in clinical trials.
More remains to be done. Merck is now conducting a large study of more than 14 500 people to confirm that the reduction in LDL cholesterol translates into fewer heart attacks and strokes, and fewer cardiovascular deaths.
Merck plans to apply to the Food and Drug Administration to market enlicitide in early 2026 and hopes to launch the drug in 2027.
See more from MedicalBrief archives:
More aggressive statin therapy sometimes needed to fight ‘bad’ cholesterol
LDL cholesterol levels must be lowered in high CVD risk patients
New, cheaper pill taken with statins lowers LDL cholesterol more