VERVE-102: One-and-Done Cholesterol Cure–Miracle or Mirage?

A study in the New England Journal of Medicine (May 25, 2026) is generating huge headlines about a cholesterol “cure.” VERVE-102 is a one-dose gene-editing therapy that is capable of producing very long-lasting LDL Cholesterol control. It has created huge enthusiasm within the cardiology community. We are reading words like “revolutionary” and “breakthrough” to describe this billion-dollar bet by the Eli Lilly company. Will the treatment live up to early expectations?

Cardiologists Love to Hate LDL Cholesterol

The cardiology community has declared war on LDL cholesterol. For decades, the Holy Grail in heart attack prevention has been to get LDL cholesterol (LDL-C) as low as possible. Ralph, a cardiology friend, once described it this way: You can’t have too low a golf score or cholesterol count. In other words, the lower the better!

Verve-102 dramatically lowered LDL cholesterol levels after a single infusion. In the highest-dose patients (1.0 mg/kilogram), LDL-C dropped by more than 60 percent and remained low for up to a year. The drug works by changing gene function in the liver.

This study is small, involving only 35 patients. It is more a proof of concept rather than a clinical trial. The target of this gene therapy is PCSK9, which is crucial to the body’s production of LDL cholesterol.

VERVE-102: Perspective From An Insider

Some of the news stories about VERVE-102 have suggested that it is a revolutionary new approach to preventing heart disease. That’s because one shot of this gene-editing therapy produces such a long-lasting result: low levels of “bad” LDL-cholesterol.

A British cardiologist who participated in the study told the BBC Science Focus (May 21, 2026):

“This is the future. This is reality; it’s not science fiction. We’re actually doing it. I’ve had patients of mine in the trial receive this one-and-done treatment and it’s going to change the face of cholesterol management going forward.

“We’re seeing some spectacular results. This drug turns off a tiny fraction of DNA, and your LDL cholesterol is lower by 50 percent for the rest of your life. That’s it. One and done. This is going to be revolutionary.”

The Latest Guidelines for LDL Cholesterol

Most cardiologists agree with my friend Ralph that the lower the LDL cholesterol levels the better. And the American College of Cardiology and the American Heart Association has issued new guidelines. They want screening to start at age 30. And they want to assess 30-year risk of heart problems rather than 10-year risk.

If you belong in the low-risk category you are supposed to have LDL cholesterol below 100 mg/dL.

If you are categorized as a higher-risk patient your doctor will likely insist that you get your LDL cholesterol levels below 70 mg/dL.

Very High Risk patients are told to get LDL cholesterol levels below 55 mg/dL.

It would be unlikely for most people to achieve such goals without a medication on board. An article in the American Journal of Cardiology (July 1, 2006) suggested that 20 years ago the average LDL cholesterol in American adults was 130 mg/dL. Perhaps that is why roughly 50 million Americans are now taking statin-type cholesterol-lowering medications.

Will VERVE-102 Help Eliminate Heart Disease?

But before anyone declares victory over heart disease, a few uncomfortable questions remain.

Cardiologists have spent many decades aggressively lowering LDL cholesterol with statins and, more recently, powerful PCSK9 inhibitors (Repatha and Praluent). Yet heart disease remains America’s leading killer. Despite the fact that so many people have been taking medications that can dramatically lower LDL cholesterol, many still develop dangerously clogged coronary arteries, suffer heart attacks or need bypass surgery, despite “ideal” LDL numbers.

That does not mean LDL cholesterol is irrelevant. Most cardiologists remain convinced that lowering LDL reduces cardiovascular risk. But critics point out that cholesterol is only one piece of a much more complicated puzzle involving inflammation, insulin resistance, blood clotting, lipoprotein(a), diet, exercise, stress, genetics and other poorly understood factors.

Drug companies love to brag about relative risk reduction (RRR). That is why the company that made Lipitor (atorvastatin) advertised its best selling drug:

“In patients with multiple risk factors for heart disease,

“Lipitor reduces risk of heart attack by 36%*”

The asterisk reveals the absolute risk reduction (ARR)”

“*That means in a large clinical study 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients of patients taking Lipitor.”

A 1% heart attack lowering effect sounds a lot less impressive than a 36% risk reduction. How to drug companies manage this math? To get the RRR you divide 1 by 3 and get a 33% risk reduction. To get the ARR you subtract 2% from 3% to get a 1% risk reduction.

I am simple minded. The asterisk from the company that developed Lipitor tells the truth. If 100 people in the clinical trial took a sugar pill for 5 years, 3% (3 out of 100) would would have experienced a heart attack. And if 100 people in that clinical trial took Lipitor, 2% (2 out of 100) would have experienced a heart attack. Therefore, I conclude that 1 person out of 100 would have benefited from atorvastatin and avoided a heart attack.

Always ask the prescriber for the absolute risk reduction number of any medicine you take. It will provide you a much more accurate assessment of how well a particular treatment works to benefit patients compared to an untreated group.

Lowering LDL Cholesterol: Relative Risk vs. Absolute Risk Reduction

An article in JAMA Internal Medicine (March 14, 2022) compared relative risk reduction with statins to absolute risk reduction.

Here are the findings:

“In this meta-analysis of 21 randomized clinical trials in primary and secondary prevention that examined the efficacy of statins in reducing total mortality and cardiovascular outcomes, there was significant heterogeneity but also reductions in the absolute risk of 0.8% for all-cause mortality, 1.3% for myocardial infarction [heart attack], and 0.4% for stroke in those randomized to treatment with statins compared with control, with relative risk reductions of 9%, 29%, and 14%, respectively.”

Meaning:

“The study results suggest that the absolute benefits of statins are modest, may not be strongly mediated through the degree of LDL-C reduction, and should be communicated to patients as part of informed clinical decision-making as well as to inform clinical guidelines and policy.”

I fear that message is not generally communicated to patients. We hear from many people that their providers often insist that if they do not take a statin they will likely experience a heart attack.

VERVE-102 and Heart Attack Reductions?

The VERVE-102 study described at the top of this article was also extremely small—just 35 patients—and was designed primarily to test safety and proof of concept, not whether people actually live longer or avoid heart attacks. Those answers could take many years.

Gene editing for cholesterol may someday transform cardiovascular medicine. But lowering a laboratory number is not the same thing as guaranteeing protection from heart disease. That distinction is easy to forget when a “breakthrough” generates headlines about a “one-and-done cure.”

The real question is not whether VERVE-102 lowers LDL cholesterol. It clearly does.

The question that matters most is far harder:

Will permanently lowering LDL cholesterol actually prevent the heart attacks and sudden cardiac deaths that patients fear most?

If so, how many people out of 100 will be protected? Will it be 1%, 10% or 50%? If I were a betting person, which I am not, I would guesstimate it would be be closer to 1 or 2% rather than 10 to 50%. Only time will tell.

The PCSK9 Inhibitor

We do have an idea how well drugs that inhibit PCSK9 and lower LDL cholesterol work to reduce heart attacks. That’s because Repatha works on the same concept as VERVE-102. It lowers LDL-C by neutralizing PCSK9. Instead of a long-lasting effect, though, this drug must be injected once every two weeks or once a month indefinitely.

The FOURIER trial was published in The New England Journal of Medicine (online March 17, 2017). There were 27,564 patients at high risk for heart disease. Many had already suffered a heart attack. LDL cholesterol was aggressively lowered with a statin and Repatha. A “control” group got statins plus placebo injections instead of Repatha. LDL cholesterol levels were reduced to around 30 in the Repatha group. That’s impressive.

The relative risk reduction after 26 months was 21 to 27 percent. But the absolute risk reduction was less than 2 percent. We are talking about heart attack, stroke or cardiovascular death. The patients who “only” got a statin experienced one of those end points 7.4% of the time. The patients who got a statin plus Repatha (evolocumab) experienced a heart attack, stroke or cardiovascular death 5.9% of the time. Do the math. The difference was 1.5%.

Final Words About VERVE-102

There is no question that VERVE-102 can dramatically lower LDL cholesterol. This gene-editing treatment is long lasting. It may even be permanent. The question I am asking goes beyond lowering LDL cholesterol, though. Will the drug save lives? How many people out of 100 will avoid a heart attack, stroke or death from cardiovascular disease if they get a VERVE-102 infusion? And what will it cost?

The headlines have been jubilant. And, as described above, one of the researchers described the outcome as “spectacular” and “one and done.” I will applaud, but only if the new compound makes a huge dent in heart attacks and deaths from cardiovascular disease.

What do you think? Please share your understanding of risk reduction in the comment section below. No matter how hard I try to explain the difference between relative and absolute risk reduction, I seem to leave readers in a daze. Would you ever ask a healthcare professional what the absolute risk reduction is for a medication they recommend?

I would very much appreciate your feedback. If you think others might benefit from this information, please send it along. Thank you for supporting our work.