Beyond Leqvio: The One-Time Cholesterol Treatment Now Heading to Phase 2
I’ve been writing on this site about how cholesterol care has changed in the last decade. We moved from daily statin pills to twice-a-month injections like Repatha, then to a twice-a-year injection called Leqvio. Each step made it easier for patients to stay on treatment, and each step cut LDL cholesterol further. Today Eli Lilly announced Phase 1 data on a treatment that might be the next step on that arc. It’s a one-time gene editor that permanently turns off the PCSK9 gene in your liver. The early numbers are strong. I want to walk you through what this is, what it isn’t, and what it would mean if it actually reaches the clinic.
The arc from statins to a single shot
Cholesterol care used to be one tool. A statin pill, every day, for the rest of your life. Statins still work, and most of my patients with elevated LDL still take one. They cut LDL by 30 to 50 percent in most people, and there are decades of evidence that they prevent heart attacks and strokes.
The problem isn’t whether statins work. The problem is whether people stay on them. About half of patients stop taking their cholesterol medication within a year of starting it. Some can’t tolerate it. Some forget. Some just don’t like the idea of a daily pill for a disease they can’t feel. That gap between what a medication can do in a trial and what it does in real life is where preventive cardiology actually lives or dies.
PCSK9 inhibitors were the first big answer to that adherence gap. Repatha (evolocumab) and Praluent (alirocumab) came out in the mid-2010s as injections you give yourself every two weeks. They drop LDL by 50 to 60 percent on top of a statin, sometimes more. For patients who couldn’t tolerate statins, or whose LDL stayed too high on a maximum-dose statin, these medications were a turning point. I’ve written more about how they work in my full guide to PCSK9 inhibitors.
Then came Leqvio (inclisiran), the second big answer. Instead of a biweekly injection, Leqvio is given twice a year in the office after the first couple of loading doses. It uses a different technology called siRNA, which quiets the PCSK9 gene rather than blocking the PCSK9 protein after it’s already been made. The result for the patient is the same idea on a longer schedule: dramatic LDL drops, lasting six months at a time. The FDA expanded the Leqvio label in July 2025 so I can now use it as a first-line cholesterol treatment, not just an add-on to a statin. I wrote about why that label change matters in this earlier post, and there’s a deeper article on Leqvio’s mechanism here.
So that’s where we’ve been. Statins daily. Antibody injections every two weeks. siRNA injections twice a year. Each step a smaller adherence burden, each step a bigger LDL drop for the patients who can reach it. Today’s news takes that arc one step further.
What Lilly announced
The treatment is called VERVE-102. It was developed by a company called Verve Therapeutics, which Lilly acquired in 2025. The Phase 1 results released today show that a single dose, given through an IV, cut LDL cholesterol by 62 percent in patients who received the highest dose. That drop was still in place 18 months later in the people who’d been followed the longest.
To put 62 percent in context, an industry analyst quoted in the news coverage said 50 percent was the bar he’d want a new cholesterol treatment to clear. Repatha cleared that bar. Praluent cleared it. Leqvio cleared it. VERVE-102 cleared it with room to spare, on a single dose, with no follow-up injection.
Lilly plans to start enrolling patients into a Phase 2 trial by the end of 2026.
What “gene editing” actually means here
This is where the language gets technical, so let me translate it.
You may have heard of CRISPR. CRISPR is a tool scientists use to cut DNA and make changes to it. The original versions of CRISPR cut both strands of the DNA double helix and let the cell’s own repair machinery patch things up. That works, but it’s a blunt change, and the patches don’t always come out clean.
VERVE-102 uses a refined version of this idea called base editing. A base editor doesn’t cut the double helix. It chemically rewrites a single letter of the DNA code into a different letter. In the case of VERVE-102, that single-letter change disables the PCSK9 gene in liver cells. The cell can no longer build PCSK9 protein. With PCSK9 out of the way, your liver’s LDL-clearing system runs at full capacity again.
If you’ve read my PCSK9 guide, the analogy I use is that PCSK9 is a toxin that clogs the natural garbage disposals in your liver cells. Repatha and Praluent grab the toxin in your bloodstream before it can clog anything. Leqvio quiets the gene’s instructions so the liver makes less of the toxin. VERVE-102 turns the gene off entirely. Same target. Different floor.
The treatment is delivered as a lipid nanoparticle that finds its way into liver cells using a sugar called GalNac. The base editor does its single-letter edit, and then the nanoparticle clears out. Inspiration for the whole approach comes from a real piece of human genetics. A small percentage of people are born with naturally non-functional PCSK9 genes. Those people walk around with very low LDL cholesterol their entire lives, plus dramatically reduced rates of heart attack and stroke. VERVE-102 is trying to give that genetic profile to people who weren’t born with it.
Why I’m cautiously excited but not throwing out my prescription pad
The 62 percent number is striking. The durability is striking. The idea of a one-time treatment for a chronic problem is genuinely new in cardiology. I’m watching this program closely.
I also want to be honest with you about where it is and where it isn’t.
This is Phase 1. Phase 1 means a small number of patients dosed mostly to check safety and find the right dose. The big efficacy and safety data come from Phase 3, which is years away if Phase 2 goes well. If everything proceeds smoothly, FDA approval is probably four to six years out. Some programs take longer. Some never get there.
There’s a hard lesson in this program’s history. Verve’s first attempt at a PCSK9 base editor was called VERVE-101. It used a different lipid nanoparticle delivery system, and the program ran into liver toxicity problems serious enough that Verve had to redesign the delivery. VERVE-102 uses a new GalNac-containing nanoparticle and has had a cleaner safety profile so far. That’s encouraging. It’s also a reminder that gene-editing programs can stumble at any point along the way.
A genetic edit is permanent. This is the cleanest difference between a base editor and any drug I currently prescribe. If you take a statin and you develop muscle pain, we stop the statin and the muscle pain goes away. If you get a Leqvio injection and have an unexpected reaction, the medication clears your system within months. If you have your PCSK9 gene edited and an unexpected long-term consequence shows up 10 years later, the gene stays edited. The whole field of in vivo gene editing is still working out how to think about that asymmetry. I want to see longer follow-up before I’d offer this to any of my patients who have decent alternatives.
It probably won’t be for most people with high cholesterol. A 65-year-old patient who needs more LDL reduction than a statin alone provides is going to get Leqvio or Repatha. A one-time gene edit doesn’t make sense at that age when an established medication will get them where they need to be. The patients most likely to benefit first are younger people with a strong genetic form of high cholesterol called heterozygous familial hypercholesterolemia, or HeFH. That’s a condition where you inherit one bad copy of the LDL receptor gene from a parent, your LDL runs very high from childhood, and your first heart attack often comes in your forties or fifties without aggressive treatment. For someone with HeFH in their thirties, a single dose that locks in lifelong LDL control has real appeal in a way it doesn’t for a 65-year-old whose statin and Leqvio are already doing the job.
Cost will be high. Other approved in vivo gene therapies have come to market priced in the millions per patient. VERVE-102 may or may not be priced that aggressively. A one-time edit is going to be expensive on day one regardless. Insurance access will be its own fight.
Where I think this fits
I tell patients that medicine is moving in two directions at once on cholesterol. The first direction is making powerful tools easier to take, so the gap between trial efficacy and real-world effectiveness shrinks. That’s the Leqvio direction. Twice a year, in the office, no daily pill burden. We’re still relatively early in figuring out which of my patients should be on Leqvio versus a statin versus both, and the data are pointing toward broader use over time.
The second direction is more ambitious. It’s about settling the LDL question once. Not for six months. Once. That’s the VERVE-102 direction. It’s not ready for the clinic yet, and it may never be the right answer for older patients with conventional cardiovascular risk. For a small group of patients with a genetic head start on heart disease, a single-shot lifelong fix is a genuinely new option. I’d rather we get there carefully than quickly. A gene edit is permanent, so the patience pays off. From the data Lilly released today, it looks like the careful path is still working.
What you should do with this news today
If you’re already on a statin and your LDL is where we want it, nothing changes. Stay on what’s working.
If you’re on a statin and your LDL is still too high, or if statins haven’t agreed with you, this is exactly the conversation Repatha and Leqvio were built for. There’s no need to wait for a gene editor that won’t be available for years. Those medicines are here today, they’re approved, they work, and we can usually get you to your goal.
If you have a strong family history of early heart attacks, especially one that suggests heterozygous familial hypercholesterolemia, this news matters more for you. Genetic testing, advanced lipid testing (apolipoprotein B, lipoprotein(a)), and a careful family history are worth doing now, regardless of what happens with VERVE-102 in trials. Patients with FH are exactly the population for whom a one-time treatment, when it eventually arrives, would matter most. Get the workup. Get the diagnosis on paper. Get into a preventive cardiology relationship that can act on whatever the next five years bring.
I’ll keep writing about this as the Phase 2 enrollment opens and the data evolve. The arc of cholesterol care has been a steady reduction in how much work a patient has to do to stay protected. We went from daily to biweekly to twice yearly. The idea that the next stop might be once, ever, is worth paying attention to.