Patients with high cholesterol, often the kind that lingers in families, stepped into a clinical trial with hopes for a different future.
In preliminary findings from a small study, a single infusion of an experimental drug called VERVE-102 has reduced levels of LDL cholesterol—often labeled as “bad cholesterol”—by up to 69%. Unlike daily medications or monthly injections, this involves a one-time genetic alteration.
“This is reality; it’s not science fiction. We’re actually doing it,” remarked Dr. Riyaz Patel, a cardiologist from University College London.
Flipping a genetic switch
Nearly half of the adult population worldwide deals with high cholesterol. While medications like statins can help lower it, they require daily intake. VERVE-102, however, is not your typical medication. It employs a technique known as in vivo base editing—essentially rewriting DNA without breaking the genetic code. This specific edit targets the PCSK9 gene, which regulates how efficiently the liver removes LDL cholesterol from the bloodstream. Fewer PCSK9 proteins lead to more LDL receptors in liver cells, resulting in less cholesterol clogging the arteries.
The early-stage trial, labeled Heart-2, involved 14 participants suffering from heterozygous familial hypercholesterolemia (HeFH), a genetic condition that causes dangerously high cholesterol levels from a young age. These patients often require lifelong treatment and still face increased risk of heart issues.
Each participant received a single intravenous infusion of VERVE-102, delivered in a lipid nanoparticle designed for direct action in the liver. There were no reported side effects or liver damage noted among the participants.
Individuals were given three different dosages:
- At 0.3 mg/kg, there was a 21% decrease in LDL cholesterol.
- At 0.45 mg/kg, the reduction averaged 41%.
- At 0.6 mg/kg, LDL cholesterol dropped 53% on average, with one participant experiencing a remarkable 69% reduction.
These results are quite promising, even if the study is still in the initial phases.
Why this could be huge
Cholesterol is vital for the body, but it can turn harmful when it builds up in arteries, creating plaques that may lead to heart attacks or strokes. Reducing LDL levels is a key strategy for preventing such outcomes.
While VERVE-102 was primarily designed for those with inherited cholesterol issues, its method—permanently shutting down the PCSK9 gene—could also help others with high LDL cholesterol. The PCSK9 gene plays an important role in how much LDL the liver can eliminate from circulation. By inhibiting this gene, cholesterol levels can be lowered for almost anyone, regardless of their genetic predisposition.
Interestingly, many existing cholesterol-lowering medications also target PCSK9. The distinguishing factor with VERVE-102 is that it aims to induce a lasting change with just one treatment.
More study is still needed
The initial results from the clinical trial have yet to undergo peer review.
The next steps will involve testing higher doses. Two participants in the 0.7 mg/kg group have already received VERVE-102, and so far, no concerns have been flagged. Verve plans to share full results from this dose escalation phase later in the year and commence a Phase 2 trial, which will include U.S. patients for the first time.
Meanwhile, Eli Lilly, the pharmaceutical giant, is monitoring the situation closely. They hold rights to co-develop and commercialize the drug should they choose to proceed. A decision on this is expected in the latter part of 2025, at which point we should also see more detailed information regarding the treatment’s effectiveness.
While not a universal cure for all high cholesterol cases, this treatment could offer significant hope for those facing the toughest challenges.
