The Victorian Heart Hospital and Victorian Heart Institute, operated by Monash Health in partnership with Monash University, have led a groundbreaking first-in-human trial of a gene-editing therapy that could permanently lower cholesterol and triglyceride levels in people with difficult-to-treat lipid disorders.
The early-stage study marks a significant milestone for cardiovascular medicine, testing the investigational compound CTX310, a CRISPR-Cas9 gene-editing therapy designed to switch off a gene called angiopoietin-like protein 3 (ANGPTL3), which is a key regulator of blood fats linked to heart disease.
In the global Phase 1 trial, 15 patients received a single intravenous infusion of CTX310, including three treated at the Victorian Heart Hospital. The therapy utilises microscopic fat-based particles to deliver CRISPR editing tools directly into the liver, where they target and disable the ANGPTL3 gene. People who are naturally born with this gene switched off have lifelong low levels of LDL (“bad”) cholesterol and triglycerides, and a much lower risk of developing atherosclerotic cardiovascular disease.
The trial's results were described as highly encouraging. Within two weeks of treatment, both LDL cholesterol and triglyceride levels fell sharply and remained low for at least 60 days. At the highest dose, CTX310 produced an average 50 per cent reduction in LDL cholesterol and 55 per cent reduction in triglycerides. Across all participants, levels of both fats fell by nearly 60 per cent.
Importantly, CTX310 is the first therapy to demonstrate substantial reductions in both LDL cholesterol and triglycerides simultaneously, offering new hope for patients with mixed lipid disorders.
Professor Stephen Nicholls, Director of the Victorian Heart Hospital and Victorian Heart Institute and the study’s lead investigator, said the results represent a potential breakthrough in preventive cardiology.
“The best way to treat heart disease, the leading cause of death for both men and women globally, is to prevent it,” Professor Nicholls said. “Gene-editing technology is a new frontier of medical treatment, and it’s incredibly exciting for Victorians and Australians that we are leading such an important trial.”
Adherence to cholesterol-lowering medication remains one of the greatest challenges in cardiovascular prevention. A one-time infusion that delivers long-term or permanent benefit could eliminate this problem. “The possibility of a single-course treatment with lasting effects could be a major step in how we prevent heart disease,” Professor Nicholls said. “It makes treatment easier, reduces ongoing costs, relieves pressure on the health system – all while improving a person’s quality of life.”
The Phase 1 study found the treatment to be safe and well-tolerated, with only minor and short-term side effects reported. No serious safety concerns have been observed to date.
Developed by CRISPR Therapeutics, CTX310 will now progress to larger, multinational trials planned for late 2025 or early 2026. These will test the therapy in more diverse patient groups and assess its long-term impact on cardiovascular outcomes.
The results were presented by Professor Nicholls at the American Heart Association Scientific Sessions in New Orleans and simultaneously published in The New England Journal of Medicine.
The Phase 1 trial involved participants aged 18 to 75 years across six sites in Australia, New Zealand and the United Kingdom, all of whom had elevated lipid levels despite maximum tolerated therapy. Patients will continue to be monitored for one year, with a 15-year long-term follow-up period, as required for all CRISPR-based therapies.
Professor Nicholls said that if confirmed in future phases, CTX310 could help save millions of lives worldwide. “This trial shows that gene-editing therapy for cholesterol and triglycerides is both possible and safe,” he said. “It could change how we think about treating and preventing heart disease for generations to come.”