Phase 1a Trial Demonstrates Sustained Lipid Reduction via CTX310 Gene Editing

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Summary of  New England Journal of Medicine https://doi.org/10.1056/NEJMc2609825
Dr. Luke J. Laffin et al.

Points

Cleveland Clinic researchers conducted a first-in-human Phase 1a clinical trial evaluating CTX310 gene editing in fifteen patients with medication-resistant lipid disorders.
The CRISPR-Cas9 therapy delivers a single infusion directly into liver tissue to switch off the ANGPTL3 gene, which regulates circulation of atherogenic lipids.
Patients receiving the highest dose tier of zero point eight milligrams per kilogram maintained a fifty-two point five percent reduction in LDL cholesterol.
Triglyceride levels decreased by forty-seven point eight percent from baseline at twelve months in participants treated with the highest therapeutic dose of CTX310.
Clinical evaluations recorded no dose-limiting toxicity or therapy-related serious adverse events, initiating a mandatory fifteen-year post-treatment safety monitoring phase.

Summary

This first-in-human Phase 1a clinical trial evaluated the safety, efficacy, and 12-month durability of CTX310, an experimental CRISPR-Cas9 gene-editing therapy designed to target and switch off the hepatic ANGPTL3 gene. Led by Dr. Luke Laffin at the Cleveland Clinic, presented at the 2026 European Society of Cardiology annual meeting, and published in the New England Journal of Medicine, the study investigated whether a single infusion of CTX310 could deliver sustained reductions in atherogenic lipids for 15 patients with medication-resistant lipid disorders.

In the trial cohort, participants received a single intravenous infusion of CTX310 across weight-based dose tiers ranging from 0.1 to 0.8 mg/kg following premedication with corticosteroids and antihistamines. At 12 months post-treatment, patients in the highest dose group (0.8 mg/kg) demonstrated a 52.5% reduction from baseline in low-density lipoprotein (LDL) cholesterol and a 47.8% reduction in serum triglycerides. Overall, the highest dose tier sustained average lipid reductions of approximately 50% across both parameters over the one-year observation period.

Safety evaluations demonstrated that CTX310 was well tolerated with no treatment-related dose-limiting toxicities or serious adverse events reported throughout the 12-month follow-up. The authors conclude that single-dose hepatic gene editing via CTX310 achieves durable, clinically meaningful reductions in ANGPTL3 and atherogenic lipids, supporting ongoing phase investigations and the mandatory 15-year FDA long-term safety monitoring protocol.

Link to the article: https://www.nejm.org/doi/10.1056/NEJMc2609825

References

Laffin, L. J., Nicholls, S. J., Scott, R. S., Clifton, P. M., Koops, R., Sarraju, A., Singh, S., Wang, Q., Wolski, K., Xu, H., Nielsen, J., Patel, N., Duran, J. M., & Nissen, S. E. (2026). Durability of crispr-cas9 gene editing targeting angptl3 with ctx310. New England Journal of Medicine, NEJMc2609825. https://doi.org/10.1056/NEJMc2609825