A first-in-human Phase 1 clinical trial demonstrated that a single infusion of an investigational CRISPR-Cas9 gene-editing therapy significantly reduced LDL cholesterol and triglycerides in adults with difficult-to-treat lipid disorders. The preliminary findings were presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans.
The therapy, known as CTX310, is designed to turn off the ANGPTL3 gene in the liver permanently. Reduced activity of this gene is associated with lower levels of LDL cholesterol and triglycerides, two major contributors to atherosclerotic cardiovascular disease. The treatment is administered as a one-time intravenous infusion, utilizing lipid nanoparticles to transport the gene-editing components to the liver.
In this trial, 15 adults between the ages of 18 and 75 received one infusion of CTX310 at ascending dose levels, with follow-up of at least 60 days for this analysis. All participants had elevated lipid levels despite maximum tolerated standard therapies. Cholesterol and triglyceride reductions were observed within two weeks of treatment and remained low throughout the follow-up period. The average decrease at the highest dose reached nearly 50% or more for both LDL cholesterol and triglycerides. Researchers noted that a reduction of 30–40% would have been considered successful for a first-in-human study.
The treatment was generally well tolerated. Three participants experienced temporary infusion-related symptoms such as back pain and nausea that resolved with medication. One participant with elevated liver enzymes at screening experienced a further temporary rise that resolved without medical intervention. No serious or long-term safety signals have been identified to date, and regulatory guidance requires extended monitoring for up to 15 years for all CRISPR-based therapeutics.
CTX310 is the first therapy to demonstrate substantial, simultaneous reductions in both LDL cholesterol and triglycerides in individuals with mixed lipid disorders, a population that often requires multiple ongoing medications. Researchers emphasized that if the effects prove durable and safe in larger studies, the approach may offer a single-treatment, long-term alternative to daily or monthly lipid-lowering medications.
The study took place from June 2024 through August 2025 at clinical sites in Australia, New Zealand, and the United Kingdom. Participants will continue to be followed for one year within the trial, with long-term safety monitoring extending to 15 years. Larger Phase 2 trials are planned for late 2025 or early 2026 to evaluate broader patient populations and long-term cardiovascular outcomes.
KEY QUOTES:
“This is really unprecedented. A single treatment that simultaneously lowered LDL cholesterol and triglycerides. If confirmed in larger trials, this one-and-done approach could transform care for people with lifelong lipid disorders and dramatically reduce cardiovascular risk.”
Luke J. Laffin, M.D., Lead Study Author and Preventive Cardiologist, Cleveland Clinic
“Adherence to cholesterol-lowering therapy is one of the biggest challenges in preventing heart disease. Many patients stop taking their cholesterol medications within the first year. The possibility of a one-time treatment with lasting effects could be a major clinical advance.”
Steven E. Nissen, M.D., FAHA, Co-Author and Chief Academic Officer, Cleveland Clinic Heart, Vascular and Thoracic Institute
“This has been a great opportunity to perform a pivotal first-in-human gene editing study of ANGPTL3 in patients in Australia and New Zealand.”
Stephen J. Nicholls, Lead Study Investigator and Director, Victorian Heart Institute at Monash University
