Gene Therapy Shows Promise in Lowering High Cholesterol

Experimental CRISPR-based treatment offers hope for those with inherited or premature heart conditions.

A new gene therapy, VERVE-102, is offering hope to individuals battling high cholesterol. Early clinical trials suggest it could significantly reduce LDL levels, especially for those with familial hypercholesterolemia or premature coronary artery disease.

Key Development

The treatment, developed by Verve Therapeutics, is currently being tested on individuals with familial hypercholesterolemia (FH) and premature coronary artery disease (CAD). According to the company’s April statement, these groups require deep and durable reductions of LDL. Initial data from an ongoing clinical trial involving 14 participants showed that a single dose led to an average 53% reduction in LDL.

Participants who received the highest dose experienced a 69% reduction in LDL. **Verve’s** statement also indicated that VERVE-102 was well-tolerated, with no treatment-related serious adverse events (SAEs) and no clinically significant laboratory abnormalities observed.

CRISPR Technology

VERVE-102 employs a modified version of CRISPR, a gene-editing system. Instead of introducing a double-stranded break in DNA, it uses “base editing” to swap out a single letter in the DNA code. This approach aims to reduce the risk of unwanted mutations.

Targeting PCSK9

This experimental therapy targets the PCSK9 gene, which regulates the number of LDL receptors on cells. When PCSK9 is overactive, it breaks down LDL receptors, causing LDL to accumulate. The new therapy aims to turn off PCSK9, particularly in the liver, to promote LDL clearance. According to the CDC, about 25% of U.S. adults have high cholesterol (CDC.gov).

Clinical Trial Progress

The treatment is administered via a single intravenous infusion. Across the trial groups, there was a notable decrease in PCSK9 activity and LDL levels within 28 days of treatment, with higher doses showing greater reductions. Currently, a fourth group of patients is being enrolled to receive an even higher dose in the United Kingdom, Canada, Israel, Australia, and New Zealand.

Verve anticipates releasing data from this phase of the trial later this year and initiating its next clinical trial with a larger participant pool. The FDA has granted the therapy “Fast Track Designation” to expedite its development and approval, suggesting U.S. participants will likely be included.

Acquisition by Lilly

In June, the drug company Lilly acquired Verve, signaling their commitment to advancing the treatment. **Ruth Gimeno**, Lilly group vice president of diabetes and metabolic research and development, said in a statement that VERVE-102 has the potential to be the first in vivo [in the body] gene editing therapy for broad patient populations and could shift the treatment paradigm for cardiovascular disease from chronic care to one-and-done treatment.

Future Outlook

While early results are promising, larger and longer clinical trials are necessary before VERVE-102 can be approved for widespread use. However, it represents a significant step forward in the potential treatment of high cholesterol and related cardiovascular diseases.