The Victorian Heart Hospital and the Victorian Heart Institute have successfully led a first-in-human trial for a breakthrough gene-editing therapy that may lower cholesterol and triglycerides in people with difficult-to-treat lipid disorders. The Victorian Heart Hospital, operated by Monash Health in partnership with Monash University, treated 3 of the 15 patients across phase 1 of the global trial.
The trial tested the CTX310™ compound, a new CRISPR-Cas9 gene-editing investigational therapy delivered as a one-time infusion. The therapy uses tiny fat-based particles to carry CRISPR editing tools into the liver, switching off a gene called angiopoietin-like protein 3 (ANGPTL3). Turning off this gene lowers LDL ('bad') cholesterol and triglycerides, two blood fats closely linked to a higher risk of heart disease.
It is known that people born with natural mutations that turn off ANGPTL3 have lifelong low cholesterol and triglyceride levels without apparent harmful effects, and a lower lifetime risk of atherosclerotic cardiovascular disease.
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, a single-course treatment with CTX310 resulted in a mean reduction of LDL cholesterol by 50 per cent and triglycerides by 55 per cent. LDL cholesterol and triglycerides were reduced by nearly 60 per cent among all participants.
Importantly, CTX310 is the first therapy to achieve large reductions in both LDL cholesterol and triglycerides at the same time, marking a potential breakthrough for people with mixed lipid disorders who have elevations in both.
Professor Stephen Nicholls, Director of the Victorian Heart Hospital, Victorian Heart Institute, and study lead investigator, said the innovative treatment could be life-changing for those at risk of heart disease.
"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 treatments remains one of the biggest challenges in preventing heart disease. The one-time infusion of CRISPR-Cas9 gene-editing therapy has the potential to eliminate that challenge, and the ongoing side-effects people may experience.
"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 clinical trial of CTX310 shows the treatment is both possible and safe for people. If confirmed in future phases and larger trials, this one-time treatment has the potential to help save millions of lives worldwide from heart disease each year."
Only minor, short-term side effects were reported, and no serious safety concerns have been observed to date.
The compound, developed by biotechnology company CRISPR Therapeutics, will now move to the next phase of research planned to begin in late 2025 or early 2026, focusing on larger and more diverse patient populations.
The trial was presented by Professor Nicholls at the American Heart Association Scientific Sessions in New Orleans and published in The New England Journal of Medicine.
About the study
- The trial included 15 adult participants aged 18-75 years with various difficult-to-treat lipid disorders, including familial hypercholesterolemia and severe hypertriglyceridemia.
- Conducted at six sites across Australia, New Zealand and the United Kingdom, including the Victorian Heart Hospital.
- Participants received CTX310 as a one-time intravenous infusion at doses ranging from 0.1 to 0.8 mg/kg.
- All participants had elevated lipid levels despite maximum tolerated therapies.
- Patients will continue to be monitored for one year in this study, with 15 years of long-term safety follow-up as required for all CRISPR-based therapies.
