The news that Eli Lilly is acquiring Verve Therapeutics is fascinating. They’re dropping around $1.3 billion to buy a company that is pioneering a permanent gene edit to reduce heart disease risk.
If Verve succeeds, we’ll essentially have a vaccine against heart disease.1
It’s bold and it’s certainly exciting. But there’s also some real risk and potential downsides here that I’m going to be keeping an eye on.
Let’s talk today about what Verve is doing - why their strategy makes sense clinically, what I’m concerned about, and what I’ll be looking for in the data from their future studies.
I wrote about Verve a year ago after they presented data at the American Heart Association Conference, which you can read about here:
The Science: PCSK9 as a Target
Verve’s core technology builds on CRISPR tech to knock out a gene called PCSK9.2
I’ve written about PCSK9 before - it’s the coolest medical story that you haven’t heard about, the journey from a newly discovered genetic variation to a drug that prevent heart attacks in about a decade.
Here’s the quick version:
PCSK9 promotes the removal of LDL receptors from liver cells.
Fewer LDL receptors = more LDL particles floating in your bloodstream.
Knock out PCSK9, and you keep those LDL receptors working overtime to clear cholesterol.
Lower lifelong LDL = fewer heart attacks and fewer strokes.
We discovered this gene because of natural outliers:
People born with over functioning PCSK9 have higher LDL and more heart disease.
People with loss-of-function PCSK9 mutations have incredibly low LDL levels and strikingly low lifetime cardiovascular risk. And, importantly, they don’t seem to suffer any consequences from PCSK9 loss of function.
So PCSK9 is a rare case - particularly in heart disease - where gene editing has a clean target. The downstream biology is well understood, and the risk of “breaking” something else seems low. At least in theory.
Why Eli Lilly Is Interested
Big Pharma has already capitalized on PCSK9 as a drug target. We have:
Monoclonal antibodies (like alirocumab and evolocumab)
Small interfering RNA (inclisiran)
And now, potentially, Verve’s one-and-done gene-editing approach
What makes Verve different is that it’s permanent. One injection, and (if it works) LDL is durably lowered for life.
They’ve shown early human data - the first study with just 10 patients, with durable LDL reduction and two deaths that raised concern, the second major study with 14 patients and a more reassuring risk profile.
The founder of Verve is Sekar Kathiresan, a giant in cardiolovascular genetics, and with their leadership team and their encouraging preliminary data, it certainly makes sense to me why Eli Lilly was willing to bet big on the long game here.
This Might Be the Future…
If it works, this could functionally be a heart disease vaccine.
Keep in mind that even in the best case scenario, Verve’s treatments aren’t going to prevent all heart disease. But they will certainly reduce the prevalence.
It’s super exciting - a one-time edit gene edit that will save tons of lives.3
And while I’m sure they won’t brand it a “vaccine” (especially in this odd political climate that we’ve found ourselves in), let’s be clear: that’s what it is.
We’re talking about genetic disease prevention at population scale.
But There are Obstacles Before We Get There
As a doctor who prescribes lipid-lowering therapies every day, I think about a few core questions:
Does it reduce hard outcomes like heart attacks, strokes, death?
What’s the long-term safety picture? And this especially matters when you can’t undo it
How much does it cost? How accessible is it to my patients?
Is it better or safer than the alternatives that I already use regularly and have longer term data to understand?
We Need Outcomes Data
LDL is a great biomarker. Lowering it is strongly linked with lower cardiovascular risk.
But when it comes to heart disease, I won’t just settle for biomarkers before being willing to prescribe a medication for a disease that we have other treatments for.
There are certainly stories of drugs that improved surrogate markers and flopped when tested on real-world outcomes.
Verve doesn’t yet have outcomes data.
Not for heart attacks. Not for strokes. Not for mortality.
And until we have outcome data, I’m going to remain cautious. I’ll be optimistic, but I won’t be ready to jump in and start treating patients with it, even if we get FDA approval.
That’s also why I’ve been cautious about prescribing inclisiran, too. Until we see real outcomes, we’re guessing. Most things that “should” work based on our understanding of the biology don’t actually work when they’re rigorously tested.
The road to hell is paved with biologic plausibility.
A One-Way Street Changes the Risk Profile
This isn’t a statin. It’s not a shot every 6 months.
This is a permanent genetic edit.
That changes the risk-benefit calculus entirely.
If a gene-editing therapy goes sideways, you can’t take it back.
So we have to be damn sure it’s safe.
The burden of proof changes when there’s no clear option to undo to the treatment or let the medication effect wear off.
The Bar Should Be Higher for Heart Disease
If this were for a rare, untreatable disease, I’d be more open to early adoption. But heart disease? The most common disease on planet Earth that I treat every single day?
We have a bunch of great options, all with reassuring safety and outcomes data:
Statins
Ezetimibe
Bempedoic acid
PCSK9 monoclonals
This isn't a condition with no treatments. We already have a ton of great tools for managing cardiovascular risk.
The burden of proof for safety and efficacy is much higher when we have so many good options. This isn’t an orphan disease.
Between all of the different drug options, most patients can get their LDL under control. The group that truly can’t? That’s a tiny subset.
And here’s the kicker: for people who are already on good lipid-lowering therapy, the residual cardiovascular risk is usually driven by:
Hypertension
Insulin resistance and diabetes
Chronic inflammation
Thrombosis risk
So yes, this drug might lower LDL dramatically. But it’s not clear how much that actually moves the needle for most people with good medical care who are dying of heart disease.
What Would I Need to See?
Before I’d recommend this to a patient, I’d need:
Robust outcomes data on heart attack, stroke, CV death, all-cause mortality
Short-term safety clarity, especially after the initial deaths in the first trial
Convincing evidence of no off-target effects
Long-term follow-up on durability and unintended consequences
It’s easy to say “we didn’t see off-target editing.”
It’s harder to say, “we have a very high level of confidence this won’t cause harm over 40 years.”
The Unknown Risks of Gene Editing
When you edit the genome, you're not just tweaking a pathway.
You're editing the body’s source code. And that comes with risks that no other drug class shares.
The two biggest concerns:
Off-target edits - the treatment might cut somewhere it wasn’t supposed to, or in a different organ than intended.
Long-term unknowable consequences of editing the genome - I’m thinking cancer, specifically.
That second one is especially hard to measure.
Cancer doesn’t happen all at once. It accumulates through sequential genetic mutations over years or decades. If we’re introducing edits into the genome, even carefully targeted ones, I am going to need a really high level of confidence that there isn’t risk of something that we won’t recognize until it’s far too late.
Verve claims they don’t see off-target edits. I hope that’s true. But what’s our confidence that there’s zero risk?
And how do you prove the absence of long-tail effects across decades?
Will Anyone Want It? And Can Anyone Get It?
Here’s the part I’ve been thinking about more than I’d like to admit: what will people actually think of this?
I have no idea what the public perception of a treatment like this will be.
But in the contemporary era, I wonder about the trust factor.
This is a whole new frontier: gene editing for prevention.
It’s one thing to offer a new therapy to someone with cancer. It’s another to say, “Hey, you’re healthy, let’s edit your DNA to prevent something you might get decades from now.”4
And even if all the science works perfectly and everyone wants it, how much is this going to cost?
Who’s going to be able to get access?
A lot of unknowns here.
Final Thought
Heart disease is common. That makes the potential market huge. But it also raises the stakes.
If Verve’s therapy really is a one-time edit that lasts for life, we need to set the bar for safety and benefit sky-high.
And my opinion is that safety bar needs to be much higher than for a daily pill or biannual injection.
The vision behind Verve is one of the most ambitious and inspiring things in all of medicine - I am genuinely and completely impressed with them. I admire the courage to be so bold.
And that should make us both excited and incredibly cautious before adopting this widely.
I’ll be hoping Verve succeeds - and eagerly anticipating more data that we can scrutinize.
Keep in mind that a vaccine doesn’t mean you can’t ever get heart disease. It’s a treatment that provides some degree of lifelong protection, exactly how much is a question that we won’t know for a really long time.
This isn’t the only thing that Verve is targeting. They also have treatments in development for ANGPTL3 and LPA. But PCSK9 is the most well validated target and it’s the one that seems closest to primetime.
Potentially, because until we have the actual data, we need to remain appropriately skeptical that everything will work the way that it “should”
To be clear, this isn’t a treatment for the masses… at first. A treatment like this starts with folks with genetic disorders of cholesterol metabolism, prior heart attacks or strokes, and strong family history. The people who are at the highest risk are the ones who have the most to gain, and so they’re always the first people who new treatments make sense for.