It sounds like something out of a Ridley Scott movie. You take a single injection, and suddenly, your genetic predisposition for high cholesterol—the kind that leads to heart attacks before you're fifty—is just deleted. That is the promise of Verve Therapeutics. Specifically, their lead candidate, VERVE-101. But the headlines lately have been messy. People are seeing trial pauses and data fluctuations and wondering why these Verve drugs don't work like the "magic bullet" we were promised in the early press releases.
The truth is way more complicated than a simple "yes" or "no."
We are talking about base editing. This isn't just standard CRISPR-Cas9 where you cut the DNA and hope for the best. This is "Search and Replace." Verve is trying to turn off the PCSK9 gene in the liver permanently. If it works, your LDL (the "bad" cholesterol) drops and stays down forever. No more daily statins. No more monthly Repatha injections. But "forever" is a long time, and the human body is incredibly stubborn when you try to rewrite its manual.
The Heartbreak of the Heart-1 Trial
To understand why some people feel like these Verve drugs don't work, you have to look at the Heart-1 clinical trial data. In late 2023, the world was buzzing. Verve released data showing that at higher doses, LDL cholesterol dropped by up to 55%. That is massive. It's life-changing.
Then 2024 hit.
The company had to pause the Heart-1 trial for its primary candidate because of a grade 3 asymptomatic liver enzyme elevation in one of the patients. Basically, the liver got angry. When your liver enzymes spike like that, the FDA and other regulators get very twitchy. For that specific patient, at that specific moment, the drug didn't work the way it was supposed to—it caused a safety scare instead.
This is the first big hurdle: delivery. Verve uses lipid nanoparticles (LNPs) to get the CRISPR machinery into the liver cells. These are the same "fat bubbles" used in the COVID-19 vaccines. But the liver is a filter. It's sensitive. If you pump too many LNPs into a human being, the immune system might freak out. This is exactly what happened with the candidate VERVE-101, leading the company to pivot toward a different delivery system called VERVE-102.
Genetics Isn't a Straight Line
Biology is messy.
🔗 Read more: Exercises to Get Big Boobs: What Actually Works and the Anatomy Most People Ignore
Sometimes Verve drugs don't work because of individual genetic "noise." Even if you have the PCSK9 gene, the way your body regulates cholesterol involves dozens of other pathways. You have the LDLR gene, the APOB gene, and environmental factors like what you ate for breakfast for the last twenty years.
Base editing is precise, but it's not a god mode.
If a patient has a mutation further downstream in the cholesterol pathway, turning off PCSK9 might only do half the job. We also have to talk about "mosaicism." This happens when the gene editor reaches some liver cells but misses others. If the "edit rate" isn't high enough, the liver keeps pumping out that pesky protein, and the patient's cholesterol doesn't budge enough to matter. It's a game of percentages.
Why the "One and Done" Narrative is Dangerous
The marketing for gene editing loves the phrase "one and done." It's catchy. It sells stocks. But for the average person with heart disease, it creates a false expectation.
- The Dose-Response Curve: In the early trials, the low doses did almost nothing. If you were in the low-dose cohort, you might've walked away thinking Verve drugs don't work. You'd be right, for that specific dose.
- Liver Regeneration: The liver is one of the few organs that can grow back. If the edited cells are replaced by unedited cells over a decade, does the effect wear off? We don't know yet. We literally don't have ten years of human data.
- Safety vs. Efficacy: Sometimes a drug "works" at lowering cholesterol but fails because the side effects are too high. If a drug gives you permanent liver damage but "fixes" your heart, did it really work? Probably not.
Dr. Sekar Kathiresan, the CEO of Verve and a world-renowned geneticist, has been very open about these challenges. He’s a guy who spent his career at Broad Institute and MGH identifying these "protective" mutations in people who naturally have low cholesterol. He knows the science is sound. But translating a natural genetic fluke into a pharmaceutical product is like trying to catch lightning in a very expensive, very regulated bottle.
The Pivot to VERVE-102
When the first drug hit a wall, Verve didn't quit. They moved to VERVE-102. The difference? A different LNP delivery system that uses a different "ionizable lipid." They are also targeting the same gene but trying to make it gentler on the liver.
If you are following the stock or the medical journals, you’ll see the term "GalNAc." This is a sugar molecule that acts like a GPS for the liver. By tagging the drug with GalNAc, they hope to use much lower doses to get the same result.
💡 You might also like: Products With Red 40: What Most People Get Wrong
This is why saying Verve drugs don't work is premature. It's a versioning problem. It’s like saying "computers don't work" because your 1995 desktop kept crashing. We are currently in the Windows 95 era of gene editing. It’s clunky, it’s prone to blue-screening, but the foundation is there.
Real World Limitations: Cost and Access
Even if the science becomes 100% perfect tomorrow, there is another reason these drugs might not "work" for the general public: the price tag.
Gene therapies are notoriously expensive. We’re talking hundreds of thousands, if not millions, of dollars per treatment. If your insurance won't cover it, or if it's only approved for a tiny sliver of the population with "Heterozygous Familial Hypercholesterolemia" (HeFH), then for 99% of people with high cholesterol, the drug effectively doesn't exist.
Honestly, it’s a bit of a biotech tragedy. You have the technology to potentially end heart disease—the world's leading killer—but the hurdles are so high that it might stay a luxury for the ultra-rich or the ultra-sick for a long time.
What Actually Determines Success?
- The Target: PCSK9 is a proven target. We know blocking it works because of drugs like Praluent.
- The Precision: Base editing is safer than standard CRISPR because it doesn't break both strands of DNA. No breaks means less chance of "off-target" mutations that could cause cancer.
- The Patient: If you have severe liver disease already, these drugs are likely a no-go.
The Verdict on Verve
Do Verve drugs don't work? Currently, they are in the "experimental" phase. They have proven they can lower cholesterol in humans significantly. They have also proven that the delivery system is finicky and can cause safety issues at high doses.
It’s not a failure; it’s a refinement.
If you’re someone looking for a solution to high cholesterol today, you’re still looking at statins, Zetia, or PCSK9 inhibitors (the injectable ones). Those work. They are boring, they are daily, but they work. Verve is playing the long game. They are trying to change the "chronic care" model into a "surgical" model. One shot, and you're done.
📖 Related: Why Sometimes You Just Need a Hug: The Real Science of Physical Touch
Actionable Steps for Navigating the Future of Heart Health
If you are tracking Verve because you or a loved one has HeFH or refractory high cholesterol, don't pin all your hopes on a single trial. Here is what you should actually do:
1. Get a Calcium Scan (CAC): Before worrying about future gene edits, know your current plaque burden. A CT scan of your heart is a much better predictor of risk than a simple blood draw.
2. Optimize Current Therapy: Most people think their "drugs don't work" because they aren't taking high enough doses of statins or aren't combining them with Ezetimibe. Modern "triple therapy" can get almost anyone to goal.
3. Watch the VERVE-102 Data: The next 12–24 months are critical. Watch for the "Pulse" trial results. If the liver enzyme spikes disappear with the new delivery system, the "Verve drugs don't work" narrative will flip overnight.
4. Check for Clinical Trials: If you have HeFH and nothing else is working, look at ClinicalTrials.gov. You might be a candidate for the next generation of these edits, but go in with your eyes open regarding the risks.
Heart disease is still a beast. Gene editing is the leash we are trying to build. It’s just taking a few tries to get the knots right.