New genome editing therapy may lower cholesterol

A genome editing therapy can sharply reduce cholesterol levels in some patients, as shown in early results from a clinical trial.

The in vivo therapy, CTX310, targets the ANGPTL3 gene in liver cells, which plays a key role in lipid regulation. Results from a phase I clinical trial showed the therapy can reduce triglyceride and low-density lipoproteins (LDLs) cholesterol levels in patients, both of which are established risk factors for atherosclerotic heart disease. CRISPR Therapeutics announced the early findings alongside its first quarter financial results for 2025.

'We are highly encouraged by the initial data from our Phase 1 trial for CTX310, which demonstrates the power of our in vivo genome editing platform to deliver paradigm changing medicines to patients with serious cardiovascular disease,' said Dr Samarth Kulkarni, chairman and chief executive officer of CRISPR Therapeutics.

The trial enrolled ten patients with high cholesterol across four dose levels, from 0.1 to 0.8 mg/kg, with data available at 30 days post-infusion. The highest dose group showed the most substantial lipid reductions. One patient with severe hypertriglyceridaemia experienced an 82 percent drop in triglycerides from baseline, while another with heterozygous familial hypercholesterolaemia saw an 81 percent drop in LDL cholesterol at day 90.

No serious treatment-related adverse events were reported across any dose level, and no significant changes in liver enzymes, bilirubin or platelet levels were observed. CRISPR Therapeutics reported that the therapy has a 'well-tolerated safety profile' and the results support 'the potential for targeted efficacy in high-risk populations'.

The therapy is delivered using lipid nanoparticles (LNPs), part of the company's liver-directed genome editing platform. ANGPTL3 natural loss-of-function mutations have previously been associated with reduced lipid levels and cardiovascular disease risk without harmful side effects on overall health, making it an attractive target for therapeutic intervention.

CTX310 joins a growing portfolio of CRISPR-based therapies. The company also reported progress on its commercialised sickle cell and beta thalassaemia treatment CASGEVY, which is now authorised at over 65 centres globally, and was recommended for use on the NHS in England in early 2025 (see BioNews 1275).

CRISPR Therapeutics plans to present further data on the CTX310 phase I trial at a medical meeting in the second half of 2025.