Genome editing therapy cuts cholesterol in half, suggests clinical trial

A genome editing therapy robustly reduces harmful cholesterol levels in patients, according to data released from a Phase I clinical trial.

New data from a Phase I clinical trial show that CRISPR Therapeutics' genome editing therapy, CTX310, effectively lowers 'bad' LDL cholesterol and triglycerides. Elevated levels of LDL and triglycerides are seen in over 25 percent of US adults and can lead to atherosclerotic cardiovascular disease and increase the risk of heart attack or stroke. The therapy uses lipid nanoparticles targeted to liver cells to suppress the ANGPTL3 gene, which is vital to lipid metabolism. The Phase I results were published in the New England Journal of Medicine and shared at the American Heart Association's Scientific Sessions 2025.

'Although it is early in the study of gene-editing therapies, the efficacy demonstrated in the current trial is highly promising and represents a potential new frontier for drug development,' said Dr Steven Nissen, senior author and chief academic officer of the Heart, Vascular and Thoracic Institute at Cleveland Clinic, Ohio.

Previous results were reported from the trial after 30 days post-infusion, when ten patients had been recruited (see BioNews 1288). The trial now includes 15 patients across six sites in Australia, New Zealand, and the UK. All participants had high LDL cholesterol, elevated triglycerides, or both, and had not responded to other medications such as statins. Results 60 days after a single two-hour infusion of CTX310 show that the therapy lowers ANGPTL3 protein levels in the blood, with a dose-dependent effect. Four patients on the highest dose continued to show reductions in LDL and triglycerides within two weeks of CTX310 infusion, with sustained reductions of 50 and 55 percent, respectively, after 60 days.

The therapy has a generally well-tolerated safety profile, with adverse effects reported as mild to moderate. The most frequently observed effect is a slight increase in liver transaminase levels. One person died during the trial, but this is believed to be due to advanced atherosclerotic disease rather than the therapy itself. As the first genome editing therapy related to cholesterol metabolism to be published in a peer-reviewed journal, cardiologists see promise in the treatment as a preventive 'one-and-done' lifetime solution for atherosclerotic cardiovascular disease.

'Half of the patients who are treated with cholesterol-lowering drugs stop taking them within a year,' said Dr Nissen. 'Rather than a once-daily pill or monthly injection, this therapy would potentially offer a one-time infusion that is safe and durable for patients with high cholesterol.'

Trial participants will continue to be monitored for up to one year post-infusion of the therapy, with additional monitoring for up to 15 years, as recommended by the Food and Drug Administration (FDA) for all genome editing therapies. In 2026, the Phase II trial of CTX310 is due to begin, with plans to focus on broader populations and longer-term outcomes.