A single CRISPR base-editing injection permanently reduces LDL cholesterol by 55%, offering a potential one-time cure for familial hypercholesterolemia.
Verve Therapeutics has reported results from a Phase Ib trial demonstrating that a single intravenous injection of a CRISPR base editing therapy can permanently reduce LDL cholesterol by 55% in patients with familial hypercholesterolemia. The results, published in Circulation, suggest that gene editing could offer a one-time cure for inherited high cholesterol and dramatically reduce cardiovascular disease risk.
The therapy, VERVE-102, uses lipid nanoparticles to deliver CRISPR base editing components to liver cells, where they inactivate the PCSK9 gene. PCSK9 normally breaks down LDL receptors on liver cells; when the gene is silenced, more LDL receptors remain active, pulling more bad cholesterol out of the bloodstream.
The trial enrolled 40 patients with heterozygous familial hypercholesterolemia (HeFH), a genetic condition affecting 1 in 250 people that causes dangerously elevated LDL cholesterol from birth. These patients face a significantly increased risk of premature heart attacks and strokes, and many require lifelong statin therapy plus additional medications.
At the optimal dose, VERVE-102 reduced LDL cholesterol by an average of 55% at 6 months, with the effect remaining stable through 12 months of follow-up. Blood PCSK9 protein levels dropped by 84%, confirming durable gene editing in liver cells.
The safety profile was encouraging. No serious adverse events related to the therapy were reported. Mild transient elevations in liver enzymes occurred in some patients but resolved within two weeks without intervention. Detailed genomic analysis showed no detectable off-target editing, a key safety concern for in vivo gene editing approaches.
Dr. Sekar Kathiresan, CEO of Verve Therapeutics and a cardiologist by training, emphasized the transformative potential. Cardiovascular disease remains the leading cause of death globally, killing 17.9 million people annually. LDL cholesterol is the primary modifiable risk factor, and despite the availability of statins and other medications, many patients fail to achieve target levels due to adherence challenges or inadequate response.
A one-time injection that permanently normalizes cholesterol could prevent millions of heart attacks and strokes worldwide. The company is planning Phase II trials and is also developing therapies targeting other genes involved in cardiovascular risk, including angiopoietin-like protein 3 (ANGPTL3), which affects triglyceride levels.